"Oedo wa Nemurenai!" is set in the Edo period of Japan and centers on the life of Seizaburo, a young man who becomes entangled in the dangerous world of espionage and political intrigue. Seizaburo, initially a carefree and somewhat aimless individual, is thrust into a complex web of power struggles when he is recruited by a secretive organization tasked with protecting the shogunate. The organization operates in the shadows, employing skilled agents to gather intelligence, thwart conspiracies, and maintain order in a time of social unrest.

The narrative unfolds as Seizaburo undergoes rigorous training to become a competent spy, learning the art of disguise, combat, and subterfuge. His missions often involve infiltrating rival factions, uncovering plots against the shogunate, and navigating the treacherous dynamics of Edo's underworld. Along the way, he encounters a diverse cast of characters, including fellow spies, corrupt officials, and enigmatic figures whose loyalties are constantly in question. These interactions reveal the moral ambiguities of his work, as he is forced to make difficult choices that challenge his sense of justice and loyalty.

A key element of the story is the tension between Seizaburo's personal growth and the demands of his role as a spy. As he becomes more adept at his craft, he grapples with the ethical implications of his actions and the toll they take on his relationships. The series also explores the broader historical context of the Edo period, highlighting the rigid class structures, political instability, and cultural shifts that define the era. Through its intricate plot and well-developed characters, "Oedo wa Nemurenai!" offers a compelling portrayal of life in feudal Japan, blending action, intrigue, and historical detail.