"Kamisama Onegai" centers around a high school student named Kakeru, who inadvertently becomes the temporary landlord of a rundown apartment building after his father disappears. The building, named Kamisama House, is inhabited by a group of eccentric tenants, each with their own quirks and supernatural connections. Among them is a mysterious girl named Mikage, who claims to be a god and enlists Kakeru’s help in managing the building and resolving the tenants' problems.

The narrative explores the daily lives and interactions of the residents, blending comedy, supernatural elements, and light drama. Kakeru, initially reluctant, gradually takes on his role as landlord, often finding himself entangled in the bizarre and often humorous situations that arise from the tenants' unique circumstances. Mikage, as a self-proclaimed deity, frequently tests Kakeru’s patience with her whimsical behavior and cryptic advice, yet her presence becomes central to the building’s harmony.

The tenants include a variety of characters, such as a ghostly girl, a cursed doll, and a man with a penchant for transforming into animals. Each tenant’s backstory and personal struggles are revealed over time, adding depth to the series. The overarching plot involves Kakeru’s efforts to maintain order in Kamisama House while uncovering the truth behind his father’s disappearance and Mikage’s true nature. The story balances episodic chapters with an underlying mystery, creating a mix of lighthearted moments and gradual narrative progression.