"Nanbaka" is set in Nanba Prison, a high-security facility designed to hold some of the world’s most dangerous criminals. The story centers on four inmates—Jyugo, Uno, Rock, and Nico—who share Cell 13. Each possesses unique skills and personalities that make them stand out. Jyugo, the protagonist, is a skilled escape artist with mysterious shackles on his wrists that prevent him from breaking free. Uno is a gambler with a sharp mind, Rock is a fighter with immense strength, and Nico is a genius chemist with a childlike demeanor. Despite their criminal backgrounds, the group often engages in comedic antics and lighthearted interactions, creating a balance between humor and tension.

The narrative explores the inmates' daily lives, their relationships with each other, and their interactions with the prison staff, including the strict but caring guard Hajime Sugoroku and the eccentric warden. As the story progresses, deeper layers of the characters’ pasts are revealed, particularly Jyugo’s connection to the mysterious organization that placed the shackles on him. This organization, known as "The Numbers," plays a significant role in the overarching plot, introducing elements of mystery and action.

The series blends comedy, action, and drama, with a focus on the inmates’ attempts to escape and the challenges they face within the prison. Flashbacks and character-driven episodes provide insight into their motivations and backstories, adding depth to the narrative. The dynamic between the inmates and the guards, as well as the evolving threat posed by external forces, drives the plot forward, creating a mix of episodic and serialized storytelling. "Nanbaka" balances its comedic tone with moments of seriousness, particularly as the stakes rise and the characters confront their pasts and the dangers surrounding them.