"Nanbaka" is set in Nanba Prison, a high-security facility designed to hold the world's most dangerous criminals. The story centers around four inmates—Jyugo, Uno, Rock, and Nico—who share Cell 13. Each possesses unique skills and eccentric personalities, making them a chaotic yet endearing group. Jyugo, the protagonist, is a young man with a mysterious past and the ability to unlock any lock, a trait that has led to numerous escape attempts. Uno is a gambler with a sharp mind and a penchant for mischief. Rock is a former fighter with immense strength and a short temper, while Nico is a cheerful and eccentric individual with a talent for creating bizarre inventions.

The narrative unfolds as the inmates navigate their daily lives in Nanba Prison, engaging in comedic antics, forming bonds with fellow prisoners, and interacting with the prison staff. The guards, including Hajime Sugoroku, the strict and formidable head guard, and his subordinates, often find themselves at odds with the Cell 13 inmates due to their constant attempts to escape and cause trouble. Despite their frequent clashes, a sense of camaraderie develops between the prisoners and guards, adding depth to their relationships.

As the series progresses, darker elements of the story emerge, particularly concerning Jyugo's past. Flashbacks reveal that Jyugo was subjected to inhumane experiments, which left him with the ability to unlock anything but also with a deep-seated trauma. These experiments were conducted by a shadowy organization, and their connection to Nanba Prison becomes a central plot point. The series balances its comedic tone with moments of tension and intrigue, exploring themes of friendship, resilience, and the consequences of one's past.

The characters' backstories are gradually unveiled, providing context for their actions and motivations. Uno's gambling addiction, Rock's violent history, and Nico's eccentricities are all explored, adding layers to their personalities. The interactions between the inmates and the guards, as well as the unfolding mystery surrounding Jyugo's past, drive the narrative forward. The series combines humor, action, and emotional depth, creating a multifaceted story that appeals to a wide audience.