Ageha Yoshina is a self-assured high school student who assists others for a fee. While returning from a job, he discovers a strange calling card with the word "Psyren" imprinted on it, left behind in a phone booth, and decides to keep it, unaware of its purpose. The very next day, Ageha finds that his classmate Sakurako Amamiya possesses the exact same calling card. When he questions her, Sakurako asks him to save her, marking the start of his troubles. Confused by the circumstances of this encounter, Ageha realizes something is wrong when Sakurako goes missing. In an attempt to figure out what is happening, he decides to call the number provided on the calling card and is asked a series of questions by a mysterious voice, ending with a final, cryptic question: "Would you like to go to Psyren?" Thus begins two teenagers' participation in a game of life or death within a strange world inhabited by monsters called Taboo. Granted the ability to use psychic powers known as PSI, the duo fight to return to the place they call home.