"Onee-chan to Imōto wa Ore no Yome" centers on the life of Itsuki, a high school student who finds himself in an unconventional living situation after his parents remarry. His new stepfamily includes two sisters: the older, mature, and responsible Nao, and the younger, energetic, and mischievous Ritsu. The story explores the dynamics of their blended family as Itsuki navigates his relationships with his new siblings, who are both strikingly different in personality and approach to life.

Nao, the elder sister, takes on a caretaker role, often looking after Itsuki and Ritsu with a calm and composed demeanor. Her nurturing nature contrasts with Ritsu’s playful and sometimes chaotic behavior, creating a balance within the household. Ritsu, the younger sister, is lively and often teases Itsuki, adding a layer of humor and lightheartedness to their interactions. Despite their differences, both sisters share a deep bond with Itsuki, which evolves as they grow closer over time.

The narrative delves into the complexities of their relationships, blending moments of comedy, drama, and slice-of-life scenarios. The story examines themes of family, love, and personal growth, as Itsuki and his stepsisters adapt to their new roles and learn to support one another. The series avoids overt romantic tension, instead focusing on the genuine connections and emotional development between the characters. Through everyday situations and heartfelt moments, the manga portrays the challenges and joys of building a family from unconventional beginnings.