The Nuevo Laredo Cartel (ヌエヴォ・ラレド・カルテル Nuevo Raredo Karuteru) is a Mexican crime syndicate and branch of the Girolamo Famiglia (ジェローラモ・ファミリア Jerōramo Famiria), an Italian-American crime syndicate based in Florida. Although based in Mexico, they also operate internationally. In the Thai branch in Roanapur, which is led by Fernando Lobos, the Girolamo Famiglia's enforcer Elvis attempted to create counterfeit U.S. bills by hiring Janet Bhai and her partner Theo to make perfect counterfeiting plates.

The Nuevo Laredo Cartel is ultimately commanded by a man called Rodrigo Guerrera, who is based in Mexico. The group is heavily involved in drug trafficking and is allied with the powerful Mexican cartel Los Eses. On the other hand, Don Girolamo is the leader of the overarching eponymous Girolamo Famiglia. Furthermore, the Floridian group is invested in money counterfeiting and uses political corruption as demonstrated when Don Girolamo visited Washington, D.C. to take a secret job from U.S. Senator Jack Bonham.

In the "Greenback Jane" arc, Elvis, who was new to Roanapur, relocated to the Thai city to hire Jane and Theo to continue perfecting their counterfeit money plates. The cartel even provided the two with high-grade materials and a Swiss printing press to truly perfect their final product. When Jane kept working two months past the deadline and $200,000 over the budget, Elvis and his men paid the two counterfeiters a visit. Impatient with Jane's time and resource usage, Elvis threatened her to hurry up by signaling one gangster to kill Theo, shocking her and angering Elvis's advisor Lobos since he had to organize the corpse removal. Elvis had his men keep Jane under surveillance and confinement, giving her a time frame of 48 hours to finish the job or face severe consequences. While playing a card game with each other outside Jane's room, one of the two gangsters got up to use the bathroom. Seizing the opportunity, Jane trapped the man in the bathroom by shutting the door tight with a computer cord and then knocked out José with the computer monitor. Exiting the building, Jane ran away but was unfamiliar with Roanapur's layout while escaping the cartel, and Elvis and his men immediately dispatched to locate Jane.

Elvis and his men arrived at the Rip-Off Church and saw her pleading with Eda at the door, and the mobster fired a warning shot from his car at the door, angering Eda. He demanded that they hand over Jane, but Eda and Revy were angered and shot back at Elvis and his men. During the shooting, Lobos waved his arms and pleaded with the women to hold their fire since the situation was a misunderstanding. Eda refused to believe this and she, Revy and Rico continued shooting at Elvis and the frightened Lobos. Yolanda joined in and shot at one of the Nuevo Laredo Cartel's cars, flipping it over. Lobos ordered the cartel to retreat from the church premises, angering an injured and restrained Elvis. Elvis was bedridden from his injuries and demanded Lobos to find and capture Jane, but the latter refused. Accordingly, he had Russell, a native Floridian member of the Nuevo Laredo Cartel under Don Girolamo, hire some muscle to kill Jane since the cowboy received info on her whereabouts from Richie Leroy. Promising that Elvis would be in the Caribbean in no time to watch the sunset with Don Girolamo, Russell commented that he came to Thailand in case Elvis ran into the exact problem that he was dealing with. At the Yellow Flag, the cowboy relayed the job to the bounty hunters, who chastised him for being very bossy for someone who was oblivious to how Roanapur operated.

As Russell's various mercenaries failed to capture Jane again and again, Lobos apologized to Dutch for the mercenaries' attack on the Lagoon Company's dry dock. In the hospital, Lobos visited Elvis, who was still adamant in hunting down Jane despite the bounty hunters' failure. Stepping outside of the room, Lobos sighed while his pistol was shown under his suit jacket, implying that he was going to purge Elvis for his cost to the cartel. Elsewhere on Dutch's PT boat, Russell managed to sneak inside the PT Boat and started wrecking the engine room, where he was confronted by Eda in a firefight. When he was held at gunpoint, he was disappointed since he wondered how he would break the news to Elvis. The nun informed him that Lobos would get rid of him, surprising the cowboy, who thought that he recognized Eda. Although she tried to dissuade him from thinking further, Russell recalled how he saw someone like her when Don Girolamo visited Washington, D.C. to meet U.S. Senator Jack Bonham at the Fontainebleau. She joked that she lied about her hometown being Alabama and was instead from Langley, Virginia. When Russell realized that she was a CIA agent due to the metonym, Eda immediately shot him in the face and killed him, ending the Nuevo Laredo Cartel's pursuit of Jane for the time being.

Upon seeing Sawyer the Cleaner again, Jane was terrified and asked in fear if Girolamo hired more people again to kill her. Much later, Jane got a call from a fellow Highwaymen member telling her that she had the option to go in hiding until Reinbach A.G. was no longer angry with her. She furiously responded that she could not stay in Roanapur since there was still a bounty on her head, indicating that the Nuevo Laredo Cartel was still after her.

The Nuevo Laredo Cartel was mentioned by Mister Chang to be waging war with the Colombian Cartel for territory in Latin America. He added that the control of drugs was leaning toward the Nuevo Laredo Cartel, mentioning that their lackey Fernando would possibly become a member of the Council in the near future.

Right after the sudden death of Miguel Navarro, a high-ranking leader in the Guadalajara Cartel, cartels across Mexico began to vie for territory. Having the most control in northern Mexico and the Mexico–U.S. border region, the Nuevo Laredo Cartel had some of its territory in Sonora encroached upon by Baja California's Tecate Cartel. To gain an advantage, the cartel's leader, Rodrigo Guerrera, made an alliance with Los Soldados (a.k.a. Los Eses) by promising its rising leader, Gris el Tigres, access to heroin from the Sierra Madre Occidental's highlands. To Nuevo Laredo's pleasure, Los Eses swiftly crushed the Tecate Cartel. Furthermore, Nuevo Laredo coerced Hotel Moscow's regional leader, Vasily Krivchenko, into ceasing business with other cartels and began providing arms and money laundering to them via Russian financial institutions. Because of the hit to the Russians' reputation and the Guadalajara Cartel (their ally), Hotel Moscow commissioned Balalaika's Vysotniki to combat the cartel. In response, Nuevo Laredo had Los Eses fight against the Russians as the former cartel's shield.

In a brief period, the two cartels then contributed to weakening the Colombian Cartel enough that they lost their seat on the Council in Roanapur. After the Colombian Cartel removed their own presence from Roanapur, Fernando Lobos was informed by Chang that he would be offered a seat on the Council, pleasing him. Meanwhile, Rodrigo Guerrera informed his subordinate Lobos that he would not mind declaring a truce with the Russians on the condition that Hotel Moscow abandon the Guadalajara Cartel as their ally. Before attending the next Council meeting to vote on the appointment of Lobos to the Council, Gris el Tigres decided to accompany Lobos to the meeting to personally speak with Balalaika. On the night of the Council meeting, Lobos arrived at The Golden Swingin Night Club and voluntarily surrendered his sidearm per the meeting customs.

When the meeting began, Lobos admitted that he was honored to be offered a position among Roanapur's most powerful bosses. Chang asked him when his representative would arrive, to which the Mexican boss replied that he heard he recently arrived at the airport. At that point, Gris arrived and sat down. Lobos subsequently listened to him explain that he started his cartel after learning of Balalaika's backstory as a discarded soldier. The two bosses began to exchange words, with Gris affirming that he would do everything in his power to crush Hotel Moscow despite his respect for them. Frustrated, Lobos warned him to be quiet because the former was the one with authority in Roanapur. Chang chimed in to say that they needed to focus on their agenda item of voting on the Nuevo Laredo Cartel's appointment to the Council. In response, Lobos relayed his boss's condition of a truce to them, but Gris vehemently disagreed with him, exclaiming that they could not expose their backs to their enemy in any part of the world.

Shocked by his declaration, Lobos sat speechless as Gris asserted that he would not forgive Hotel Moscow and only wanted to kill Vasily Krivchenko because he ran Hotel Moscow's operations in Cananea. Though he could not say anything due to his shock, he snapped out of it when Rock volunteered to speak up and propose a compromise. Hearing Rock's idea that Hotel Moscow would give up its share of territory that they took after the Colombian Cartel fled Roanapur in exchange for sparing Krivchenko, Lobos agreed to the terms. When Balalaika said that she would not take a backseat to Nuevo Laredo, he assured her that the initial plan would be for his cartel to not take any shares so that the Russians had time to think about the overall deal. To his surprise, Gris interrupted them and asked Lobos if he was done with his "fairy tale." Gris declared that he would not stop at taking Krivchenko's head, causing Lobos to shout at him, but the former only replied that Lobos seemed to forget that Mexico's criminal underworld was an unforgiving place. Once Gris reiterated his threat to crush anyone who got in his way, Lobos stood up while his ally stated that war would commence after leaving the nightclub.

While in Washington, D.C., Don Girolamo acquired a job from Senator Jack Bonham to retrieve the latter's sexual blackmail tape from Leon Miller, a criminal who planned on giving the tape to Bonham's rival in the Senate. Girolamo decided to let Russell take on the job, so the cowboy broke into Miller's storage of blackmail material in a building near 14th Street. As he finally found Bonham's tape, Russell was suddenly confronted by a guard and had to dodge his attacks. He was pushed to the ground as Miller and his girlfriend arrived on the scene, prompting Russell to immediately flee the room and the building. The cowboy ran across 14th Street to avoid Miller, who was killed seconds later by a speeding semi-truck in the busy traffic. Although the Floridian secured the tape, Bonham was furious with Russell and blamed him for Miller's death revealing the blackmail collection to the police and therefore possibly exposing his own tape.

Russell assured him that he had it, not the police or media, and promised to deliver it to his intermediary. However, on the way to get the tape from its hiding place, the cowboy was abducted by two bodyguards of Bonham's rival senator. Being tied to a chair, the cowboy remained calm as he was interrogated and threatened by the rival senator, who claimed they could get along peacefully if he handed over the tape. In response, Russell bluffed and stated that the tape would be given to the media so that the blackmailers could not use it. Though skeptical, the senator ordered his bodyguard Cyrus to accompany Russell to get the tape and return it to him in exchange for the cowboy going free.

Sitting in the back of a car, Russell attempted to trick Cyrus into lowering his guard by feigning sickness and pain, but the bodyguard ignored him. When the cowboy crouched forward, Cyrus grabbed his head to force him back up, but Russell intentionally did so to let his hat fall off of his head. Grabbing the hat as he rose his upper body, he shoved it into Cyrus's face and then elbowed it, dispersing a smoke powder which disoriented him. Russell then immediately put the zip-tie around his hands in front of the driver's neck to choke him, forcing the driver to crash. He exited the car promptly and fled the scene, escaping their grasp. After retrieving the blackmail tape, Russell went to the Fontainebleau to meet Bonham in person because of his circumstances and since he heard about Bonham's meeting at the restaurant from the senator's secretary. Once inside, Russell briefly spotted Eda as she and her CIA colleagues finished their meeting with Bonham, being surprised by her appearance and navy-blue dress.

Finishing his goodbyes to the CIA agents, Bonham spotted Russell and was angry that he showed up in person, ruining the initial plan of discreetness. The cowboy explained his situation and admitted that he knew the blackmail tape's content was sexual in nature, shocking the senator. Nonetheless, he tossed the duffel bag containing the tape to the senator, advising him not to look down upon professionals whom he hired. Later that day, Russell was elsewhere in D.C. when Cyrus found him and forced him to walk to the base of Key Bridge at gunpoint. Putting his gun away, Cyrus professed that he was fired by the rival senator for failing to complete the task of acquiring the tape. To the skeptical Russell's interest, Cyrus showed that he also had a blackmail tape of his ex-boss, willing to share the profits of it if he could connect him to Bonham. As Russell admitted his hesitancy about the deal, a detached car bumper fell from the bridge and flew right at Cyrus's head, knocking him out. Seizing the opportunity, Russell took the rival senator's tape from the unconscious bodyguard and gave it to Bonham for more money, pleasing both the senator and Don Girolamo.