"Ōoku: The Inner Chambers" is set in an alternate Edo-period Japan where a mysterious disease, the Redface Pox, has drastically reduced the male population, leaving women to assume dominant roles in society. The shogunate, now led by a female shogun, governs the nation, and the Ōoku, the inner chambers of Edo Castle, becomes a space where men are confined as concubines to serve the shogun. The series explores the political, social, and personal dynamics within this gender-reversed hierarchy.

The narrative begins with the introduction of Yunoshin Mizuno, a young samurai who enters the Ōoku as a concubine to support his impoverished family. His arrival coincides with the reign of Yoshimune Tokugawa, the eighth shogun, who seeks to reform the Ōoku and uncover its secrets. Yoshimune is portrayed as a pragmatic and forward-thinking leader, determined to understand the origins of the Redface Pox and the true nature of the Ōoku's power structure. Her investigations reveal the chamber's dark history, including the exploitation and manipulation of men within its walls.

As the story progresses, the focus shifts to the relationships and power struggles within the Ōoku. Key figures include Kasuga no Tsubone, the head chamberlain, who wields significant influence over the inner chambers, and Arikoto, a high-ranking monk who becomes a confidant to Yoshimune. The series delves into the complexities of loyalty, ambition, and survival, as characters navigate the rigid hierarchies and shifting alliances of the Ōoku.

The Redface Pox serves as a central plot device, driving the societal changes that define the series. Its origins and the shogunate's response to the crisis are gradually unveiled, highlighting the tension between tradition and reform. The series also examines themes of gender roles, power dynamics, and the consequences of societal upheaval, presenting a nuanced portrayal of a world where established norms are upended.

Through its exploration of the Ōoku's inner workings and the broader implications of the Redface Pox, "Ōoku: The Inner Chambers" offers a thought-provoking narrative that intertwines historical fiction with speculative elements. The characters' struggles and the societal transformations they experience provide a compelling backdrop for examining the intersections of power, identity, and human resilience.