"Kami no Manimani" is a manga series that blends elements of comedy, romance, and supernatural themes. The narrative centers around a high school student named Kakeru Sakuragi, who discovers that his childhood friend, Miharu Hiyoshimatsu, is actually a god. Miharu, who had disappeared years earlier, returns to Kakeru's life under unusual circumstances, revealing her divine nature and her mission to protect humanity from malevolent spirits known as "Kegare."

The story unfolds as Kakeru becomes entangled in Miharu's divine duties, often serving as her reluctant assistant. Despite her godly status, Miharu retains a playful and mischievous personality, frequently causing chaos in Kakeru's life. Their dynamic is further complicated by the presence of other gods and supernatural beings, each with their own agendas and powers. Among them is Miharu's rival, the god Tsukuyomi, who often clashes with her over their differing approaches to handling Kegare.

As the series progresses, Kakeru and Miharu face various challenges, including battles against powerful Kegare, the complexities of human emotions, and the moral dilemmas that arise from interfering in mortal affairs. The narrative explores themes of responsibility, friendship, and the blurred lines between the divine and the human world. Kakeru's growth is a key element, as he transitions from a skeptical bystander to an active participant in Miharu's divine mission, often questioning the ethics of her actions and the consequences of their interventions.

The supporting cast includes other students and gods who add depth to the story, such as Kakeru's classmates who remain unaware of Miharu's true identity, and other deities who either aid or hinder the protagonists. The series balances its supernatural elements with slice-of-life moments, creating a mix of humor, action, and emotional depth. The interplay between Kakeru and Miharu forms the core of the narrative, with their evolving relationship driving much of the plot's progression.