Takumi Tsuzuki is a high school student who attends Umenomori Private Academy tuition-free, alongside his childhood friend Fumino Serizawa, who habitually says the opposite of what she feels. He spends most of his school hours fending off Chise Umenomori, the board chairman's granddaughter and a pampered princess, who constantly drags him into her eccentric hobbies. After school, he works at the "Stray Cats" confectionery, a cake shop run by his adoptive older sister, Otome Tsuzuki, until bedtime. This constitutes Takumi's average daily routine and life. Mayoi Neko Overrun follows another seemingly ordinary day in Takumi's life. With his sister away from the shop to help someone else in need, Fumino takes it upon herself to wake him up so he won't be late for their usual walk to school together, giving him a glimpse of her blue and white striped panties in the process. What a nice way to start the day. When Otome returns home, she brings with her a girl named Nozomi Kiriya, whose hair and mannerisms resemble those of a large cat. It turns out she is a runaway that Otome cannot help but take in. Takumi's ordinary days are transformed into splendid chaos as he tries to unravel who this mysterious beauty is and what she is running away from...