"Gangsta" is set in the fictional city of Ergastulum, a lawless haven for criminals, mercenaries, and outcasts. The city is divided by power struggles between various factions, including the mafia, corrupt police, and a clandestine organization known as the Monroe Family. The story centers on the Handymen, a duo of freelance problem-solvers who take on jobs ranging from errands to assassinations. The Handymen consist of Nicolas Brown, a deaf swordsman with superhuman strength due to being a "Twilight"—a person enhanced by a drug called Celebrer—and Worick Arcangelo, a charismatic gigolo and gunman with a mysterious past tied to the city's underworld.

The narrative explores the lives of Nicolas and Worick as they navigate the dangerous dynamics of Ergastulum. Their partnership is tested when they encounter Alex Benedetto, a former prostitute fleeing from the Monroe Family. Alex becomes entangled in their world, seeking refuge and a new purpose. As the trio forms an uneasy alliance, the story delves into their individual backstories, revealing the trauma and violence that shaped them. Nicolas's past as a test subject for Celebrer and Worick's complex relationship with the mafia, particularly his estranged father, are key elements of the plot.

The Monroe Family, led by the enigmatic Daniel Monroe, plays a central role in the unfolding conflict. The organization controls the production and distribution of Celebrer, a drug that grants enhanced abilities but shortens the lifespan of its users. The Handymen find themselves increasingly at odds with the Monroe Family and other factions, including the Cristiano Family, a rival mafia group, and the Hunter, a rogue Twilight assassin. The series examines themes of loyalty, survival, and the moral ambiguity of living in a city where violence and exploitation are commonplace.

As tensions rise, the fragile balance of power in Ergastulum begins to crumble. The Handymen are drawn into a larger conspiracy involving the origins of Celebrer, the exploitation of Twilights, and the city's systemic corruption. The story builds toward a climactic confrontation that forces Nicolas, Worick, and Alex to confront their pasts and make difficult choices about their futures. "Gangsta" combines action, drama, and character-driven storytelling to present a gritty and immersive narrative set in a morally complex world.