Inugami-san and Nekoyama-san, two teenage girls with differing personalities, unexpectedly find themselves drawn to each other. Inugami, the outgoing cat-lover, is determined to win over Nekoyama, the reserved dog-lover, but this only leads to chaotic responses. Despite this, their attraction grows and they become closer. Along with their shy classmate Nezu, they join the biology club and meet chilled upperclassman Ushikawa. As Nezu and Nekoyama's relationship develops, a playful game of cat and mouse ensues. The comical Inugami-san to Nekoyama-san follows the lively, explosive journey of these girls with their unusual bond.