The series follows Sho Izuta, a first-year student at Tsuna Nagai High School, a school noted for its focus on the sciences. He is also aiming to revitalize the school's Biology Club. He becomes involved with his classmate Rio Iwama after the two decide to investigate a mystery regarding a popular legend at school. According to legend, students who witness two cherry blossom trees near the school form a heart shape will become a couple. However, after reports spread that no one had seen the heart shape in recent times, the pair decide to investigate further. The two, along with the other members of the Biology Club, also become interested in the school's mysteries, aiming to solve them through the use of scientific methods.