Unlike many schools, attending Hyakkaou Private Academy prepares students for their time in the real world. Since many of the students are the children of the richest people in the world, the academy has its quirks that separate it from all the others. By day, it is a normal school, educating its pupils in history, languages, and the like. But at night, it turns into a gambling den, educating them in the art of dealing with money and manipulating people. Money is power; those who come out on top in the games stand at the top of the school. Yumeko Jabami, a seemingly naive and beautiful transfer student, is ready to try her hand at Hyakkaou's special curriculum. Unlike the rest, she doesn't play to win, but for the thrill of the gamble, and her borderline insane way of gambling might just bring too many new cards to the table.

Joutarou Kuujou and his allies have finally made it to Egypt, where the immortal Dio awaits. Upon their arrival, the group gains a new comrade: Iggy, a mutt who wields the Stand The Fool. It's not all good news however, as standing in their path is a new group of Stand users who serve Dio, each with a Stand representative of an ancient Egyptian god. As their final battle approaches, it is a race against time to break Joutarou's mother free from her curse and end Dio's reign of terror over the Joestar family once and for all.

Nanba is the world's most formidable prison, built to incarcerate criminals who are too slippery to stay in ordinary confinement. The four inmates who occupy Cell 13 are particularly cunning on that behalf, having escaped every other prison with a perfect success rate. There is Juugo, a specialist in locks who has spent the majority of his life in prison; Uno, a gambler with great intuition; Nico, an otaku whose body reacts strangely to drugs; and Rock, a bruiser with a love for food. The daily shenanigans of the four prisoners always cause trouble for the building supervisor, Hajime Sugoroku, who desperately tries to prevent them from breaking out of Nanba. Nanbaka follows the comedic, sparkle-filled exploits of these prisoners and their guards. From three square meals a day to sports festivals, prison life in Nanba isn't actually that bad—and it is the closest these four have to a home.

With World War II right around the corner, intelligence on other countries' social and economic situation has become a valuable asset. As a result, Japan has established a new spy organization known as the D Agency to obtain this weapon. Under the command of Lieutenant Colonel Yuuki, eight agents have been assigned to infiltrate and observe some of the most powerful countries, reporting on any developments associated with the war. In order to carry out these dangerous tasks, these men have trained their bodies to survive in extreme conditions and studied numerous fields such as communications and languages. However, their greatest strength lies in their ability to manipulate people in order to obtain the information necessary to give their nation the upper hand.