Once again, the Game Master's world of quests unexpectedly pulls in Yuusuke Yotsuya and the rest of this old team. Accompanied by the newest addition, Keita Torii, the team reunites with Kahabell, still unaware of their actions' impact on this world. After bidding Kahabell farewell, the team sets out on their newly appointed quest—an offering of a Jiffon Buffalo at Vaikdamnia on Jiffon Island. However, as their journey to the island commences, the team shortly finds that the quest is not as simple as it initially seemed. In fact, the island is terrorized by orcs that have made a deal with its inhabitants: instead of devouring the islanders, the orcs will be granted buffalo. With the growing shortage of buffalo, the annual Vaikdamnia festival cannot proceed. But, given the importance of the team's quest, they are left with the obvious choice—rid the island of the orcs and save the islanders.

Angelise Ikaruga Misurugi is the first princess of the noble Misurugi Empire. The kingdom has seen great power and prosperity due to the advancement of the revolutionary technology known as Mana, an abstract bending of light that has reduced the world's problems of war and pollution to a timeless peace. However, not all are blessed with the ability to wield Mana. Those who cannot are labeled Norma, outcasts of society who are considered a threat to civilization and live under constant persecution, and Angelise herself is one of many who want the Norma exterminated. But as Angelise's sixteenth birthday commences, it is discovered in a shocking revelation that she is actually a Norma. Chaos ensues, the public is outraged, and the once adored princess is exiled to Arzenal: a remote military base where Normas are forced into conscription. Now, the former royal must adapt to a harsh and vastly different lifestyle; piloting mechanical robots known as Paramail to fend off large, devastating beasts referred to as DRAGONs. However, a sinister truth about these savage creatures threatens to change everything.

In the light of day and in the dead of night, mysterious horrors await in the darkest shadows of every corner. They are unexplainable, inescapable, and undefeatable. Be prepared, or you may become their next victim. Sit back in terror as traumatizing tales of unparalleled terror unfold. Tales, such as that of a cursed jade carving that opens holes all over its victims' bodies; deep nightmares that span decades; an attractive spirit at a misty crossroad that grants cursed advice; and a slug that grows inside a girl's mouth. Tread carefully, for the horrifying supernatural tales of the Itou Junji: Collection are not for the faint of heart.

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.