"Onigawara Yokocho Sancho-me" is a manga series set in a bustling, supernatural district where humans and yokai coexist. The narrative centers around a young man named Shintaro, who inherits a small, rundown shop in the heart of Onigawara Yokocho, a mysterious alleyway filled with eccentric characters and otherworldly phenomena. The shop, which specializes in selling odd and magical items, becomes the focal point for various strange occurrences and encounters with yokai, spirits, and other supernatural entities.

Shintaro, initially skeptical and overwhelmed by his new surroundings, gradually adapts to the peculiarities of the district. He forms relationships with the locals, including a mischievous fox spirit named Kitsune, who becomes his guide and occasional troublemaker, and a reserved but powerful onmyoji named Ayame, who assists him in navigating the dangers of the yokai world. Together, they tackle a series of episodic challenges, ranging from resolving disputes between yokai and humans to uncovering the hidden secrets of Onigawara Yokocho itself.

The plot unfolds through a mix of episodic adventures and an overarching mystery surrounding the origins of the district and Shintaro's connection to it. As Shintaro delves deeper into the alley's history, he discovers that his family has a long-standing legacy tied to the balance between the human and yokai realms. This revelation brings both responsibility and danger, as he becomes a key figure in maintaining harmony within Onigawara Yokocho.

The series balances humor, action, and supernatural intrigue, with a focus on the interactions between its diverse cast of characters. Themes of coexistence, identity, and the blending of human and yokai worlds are explored through Shintaro's growth and the evolving dynamics of the district. The manga's episodic structure allows for a variety of stories, each contributing to the larger narrative while showcasing the unique charm and challenges of life in Onigawara Yokocho.