In the dual worlds of Yozakura Quartet, humans coexist with youkai, mystical beings with animal-like features and unique powers. Sakurashin, a city within a protective barrier of Seven Pillars, serves as a haven for both species. Akina Hiizumi, head of the Hizumi Life Counseling Office, wields the ancestral ability of 'tuning' to banish unruly youkai. Alongside him are Hime Yarizakura, the young youkai mayor; Ao Nanami, the town's telepathic announcer; and Kotoha Isone, a half-youkai with object-summoning skills. As the group faces new challenges and arrivals, they must safeguard Sakurashin's harmony, defending the delicate peace between humans and youkai.