"Onii-chan wa Watashi Senmon ♡ Ecchi na Doctor" centers around the relationship between siblings Haruto and Koyuki, who reunite after years of separation. Haruto, a medical student, moves in with his younger sister Koyuki, who has grown into a beautiful and confident young woman. Koyuki, now a doctor specializing in sexual health, uses her medical expertise to help Haruto navigate his insecurities and anxieties, particularly those related to intimacy and relationships. The story explores their evolving dynamic as Koyuki employs unconventional methods to "treat" Haruto's issues, often blurring the lines between professional and personal boundaries.

The narrative delves into themes of sibling bonds, personal growth, and the complexities of human relationships. Koyuki's bold and assertive personality contrasts with Haruto's more reserved and awkward demeanor, creating a dynamic that drives much of the story's humor and tension. As the series progresses, the siblings' interactions become increasingly intimate, raising questions about the nature of their relationship and the ethical implications of Koyuki's methods.

Supporting characters, including colleagues and patients, provide additional layers to the story, offering insights into the challenges and responsibilities of working in the medical field. The series balances comedic moments with more serious explorations of psychological and emotional struggles, creating a multifaceted narrative. While the premise is rooted in a romanticized and exaggerated portrayal of sibling dynamics, it also touches on broader themes of self-discovery and the importance of communication in overcoming personal obstacles.