"ONIMAI: I'm Now Your Sister!" centers on Mahiro Oyama, a reclusive 20-year-old NEET (Not in Education, Employment, or Training) who has withdrawn from society, spending his days playing video games and avoiding responsibilities. His life takes an unexpected turn when his younger sister, Mihari, a brilliant scientist, visits him and offers a mysterious drink. Upon consuming it, Mahiro undergoes a startling transformation, waking up to find himself in the body of a teenage girl. Mihari reveals that the drink was an experimental gender-swapping serum she developed, and she insists that Mahiro embrace this new identity as her younger sister.

Reluctantly, Mahiro adapts to his new life, enrolling in Mihari’s high school under the name Mahiro Oyama. The series explores Mahiro’s struggles with his new identity, navigating the challenges of adolescence, school life, and social interactions from a fresh perspective. As Mahiro interacts with classmates, including the cheerful and supportive Asahi, the reserved but kind Kaede, and the energetic Momiji, he begins to experience personal growth and a renewed sense of purpose. The narrative balances comedic moments with heartfelt reflections on identity, self-discovery, and the complexities of human relationships.

Mihari plays a pivotal role as both the catalyst for Mahiro’s transformation and a guiding figure, offering support while occasionally teasing him about his new circumstances. The dynamic between the siblings evolves as Mahiro learns to appreciate Mihari’s efforts to help him break out of his shell. The series also delves into themes of acceptance and the fluidity of identity, as Mahiro gradually comes to terms with his new reality and the opportunities it presents. Through its blend of humor, slice-of-life elements, and character-driven storytelling, "ONIMAI: I'm Now Your Sister!" offers a unique exploration of personal transformation and the journey toward self-acceptance.