Ageha Yoshina is a self-assured high schooler who assists people for a price. Returning from a gig, he spots an odd calling card bearing the word "Psyren" abandoned in a phone booth and pockets it, clueless about its function. The following day, Ageha learns that his classmate Sakurako Amamiya holds the identical calling card. Upon questioning her, Sakurako begs him to save her, marking the start of his troubles. Baffled by this meeting, Ageha senses something is amiss when Sakurako vanishes. Trying to understand the situation, he dials the number on the card and is questioned by a mysterious voice, which concludes with a final, enigmatic query: "Would you like to go to Psyren?" This initiates the two teens' involvement in a life-or-death game set in a bizarre world populated by monsters known as Taboo. Endowed with psychic abilities called PSI, the pair battles to get back to their home.