"Boku no Imōto wa 'Ōsaka Okan'" is a short-form anime series that humorously explores the cultural and linguistic differences between the Kansai and Kanto regions of Japan through the interactions of its main characters. The story centers on a high school boy who moves from Tokyo to Osaka and struggles to adapt to the local dialect and customs. His younger sister, who has fully embraced the Osaka lifestyle, becomes his primary guide and source of both support and frustration.

The narrative unfolds in a series of comedic vignettes, highlighting the brother's attempts to understand and navigate the unique quirks of Osaka culture, from its distinctive dialect to its food and social norms. His sister, fluent in the Osaka dialect and deeply ingrained in the local culture, often teases him for his lack of familiarity while simultaneously helping him adjust. The dynamic between the siblings serves as the core of the series, with their playful banter and contrasting personalities driving much of the humor.

Supporting characters, including classmates and neighbors, further emphasize the cultural divide, often providing additional comedic scenarios that showcase the brother's ongoing struggles. The series uses these interactions to offer a lighthearted yet insightful look at regional differences in Japan, blending humor with cultural education. The episodic structure ensures that each segment focuses on a specific aspect of Osaka life, making the series both entertaining and informative for viewers unfamiliar with the region's distinct identity.