Are all A Types kind yet indecisive? Does being a B Type imply the opposite? Are O Types more passionate and childish than others? How would one even get along with AB Types? Ketsuekigata-kun! explores Japanese and Korean cultural stereotypes associated with blood types in romantic and leisurely situations.

Is asking an A Type for cold medicine the best on sick days? What does a B Type wish for on New Year's? Can an AB Type really outsmart a demon? What are O Types like when they end up in the hospital? Which type has the best plan for the dreaded Valentine's Day and White Day at the office scenario? Find out the answers to these typical situations and more in the fourth season of Ketsuekigata-kun!

After unknowingly participating in a kidnapping, college student Yuuya Nomoto finds his friends brutally murdered by Hitomi Uzaki, the high school girl they attempted to abduct. Forced to drive her to an undisclosed location, he finds himself being wagered as the prize for a death match between two Therianthropes, superpowered human-animal hybrids created through advanced gene therapy. As one of these hybrids, Hitomi uses the speed and fearlessness she gained from her ratel genes to viciously dispatch her foe and save Yuuya from certain death. Waking up hours later hoping the whole event was only a nightmare, Yuuya realizes that he has become embroiled in a secret proxy war between four large Japanese business conglomerates, with the winner taking control of the economy. As her sole albeit unwilling investor, his life is now directly linked to Hitomi's ability to participate in underground bloodsport matches known only as Killing Bites.

Three years into the war, Mahito Maki loses his mother in a tragic fire at the hospital. Shortly thereafter, his father marries Natsuko, the younger sister of Mahito's mother. They take Mahito out of Tokyo to seek refuge in his late mother's rural family home. There, Mahito is constantly taunted by a strange gray heron, who seems to have taken an interest in him. Unable to come to terms with his loss and struggling to adjust to a new life in an unfamiliar place, the boy is shocked to discover that Natsuko is pregnant. To make matters worse, the pesky heron can speak—and claims that Mahito's mother is still alive. Luring him into a mysterious tower near the residence, the heron says that Mahito can save her from death, but the boy is not easily swayed. When Natsuko disappears one day, however, Mahito watches her walk into the tower and becomes compelled to venture in to rescue her. He soon finds himself falling into another world below his, where life and death seem to be entwined. As he navigates through this foreign realm to find Natsuko, Mahito must understand what it means to live if he wants to safely return home.