"Otoko no Ko Ojō-sama" centers around the life of Itsuki Ijuuin, a young man from a wealthy and prestigious family who is forced to cross-dress as a woman due to his family's strict traditions. The Ijuuin family has a long-standing custom where the eldest son must live as a woman until the age of 18 to protect themselves from a supposed curse. Itsuki, raised as a refined and elegant "ojō-sama," navigates the challenges of maintaining this facade while attending an elite all-girls school. Despite his discomfort, he excels in his role, earning admiration from his peers for his grace and beauty.

The story explores Itsuki's internal conflict as he grapples with his dual identity. While he outwardly embodies the ideal of a perfect lady, he secretly yearns to live as his true self. His life becomes more complicated when he develops feelings for a classmate, Mizuho Kujo, who is unaware of his true gender. Mizuho, a kind and straightforward girl, becomes a source of emotional support for Itsuki, further blurring the lines between his public and private personas.

As Itsuki approaches his 18th birthday, the pressure to reveal his true identity intensifies. The narrative delves into themes of identity, societal expectations, and the struggle for self-acceptance. Itsuki's relationships with his family, particularly his overbearing mother and supportive younger sister, add depth to the story, highlighting the complexities of familial duty and personal freedom. The series balances moments of humor and lightheartedness with poignant reflections on the challenges of living a double life, creating a compelling exploration of gender roles and individuality.