"Boku wa Imōto ni Koi o Suru" centers on the complex and taboo relationship between Yori and Iku, fraternal twins who develop romantic feelings for each other. The narrative explores their emotional struggles as they grapple with societal norms, familial expectations, and their own conflicting desires. Yori, the older brother, is protective and deeply devoted to Iku, while Iku, the younger sister, is initially more reserved but gradually becomes more assertive in her feelings. Their bond intensifies as they navigate the challenges of adolescence, including school life, friendships, and the growing awareness of their forbidden attraction.

The story delves into the psychological and emotional turmoil of the siblings as they confront the moral and ethical implications of their relationship. Their interactions are marked by moments of tenderness, confusion, and guilt, as they struggle to reconcile their love with the societal taboo against incest. Secondary characters, such as classmates and family members, add layers of complexity to the narrative, often serving as catalysts for the twins' internal conflicts or providing contrasting perspectives on love and relationships.

As the plot progresses, Yori and Iku face increasing pressure to conform to societal expectations, leading to moments of separation and reconciliation. The manga does not shy away from portraying the raw and often painful emotions associated with their situation, creating a narrative that is both provocative and introspective. The story ultimately examines themes of love, identity, and the boundaries of human relationships, presenting a nuanced portrayal of its central characters and their journey.