Based on the manga series 3x3 Eyes, the game tells the story of a young man named Yakumo Fujii. He lives in Tokyo and enjoys a life of an average teenager: he studies in school, works as a waiter on a part-time job, hangs around with friends, and so on. But one day, he meets a mysterious girl named Pai. Pai is the sole survivor of an ancient race called "sanzhiyan" (Chinese for "three eyes"). Long ago, they discovered the secret of immortality, but as a result they lost their human form, and some of them mutated into horrible demons. Pai's dream is to become human again. Yakumo's father was her trusty friend, but he died, and wished his son would continue helping Pai. At first Yakumo doesn't feel very enthusiastic about that, but through a bizarre accident his nature becomes inseparable from Pai's, and he becomes immortal himself. He has no choice but to help Pai. They travel around the world, from Hong-Kong to Mexico, seeking their lost humanity, and fighting the remains of the demonic race.
3x3 Eyes: Seima Kōrinden is a Japanese-style RPG set in modern times. Player-controlled characters can travel from location to location by plane, or riding Pai's winged demon. On their journey Yakumo and Pai meet other characters who join the party, and visit cities and dungeons, where they fight enemies in turn-based style. Battles are viewed from first-person perspective. Every character has various spells and techniques which can be used in battles.