Twenty-two-year-old office worker Mai Yashiro leads a perfectly ordinary life until a mysterious video game console arrives in her mailbox. Without warning, she is forcibly enrolled in a deadly game called Nightmare. The rules are brutally simple: refusing to play results in the immediate death of her loved ones, while losing a battle within the game causes parts of her own body, such as an arm, leg, or voice, to cease functioning in reality. The ultimate cost is the loss of her heart, which would mean death.

The horror of Nightmare quickly spreads throughout society, revealing that countless others are also trapped in this life-or-death struggle. In response, the company where Mai works establishes a specialized Nightmare Strategy Team. Mai is assigned to this team and relocated to a dormitory housing other players, where she discovers that her anonymous in-game benefactor, Asagi Taisuke, is not only a fellow resident but also harbors deep feelings for her that date back to their middle school days, though Mai cannot remember him. The team is divided into specialized roles: the Main Force strategizes how to complete the game, the Scouts recruit new players, and the Rescuers fight to retrieve body parts that other players have lost.

As Mai learns the mechanics of Nightmare, she encounters a legendary Japanese urban legend, the slit-mouthed woman named Amelie. After defeating Amelie in a brain battle, Mai transforms the fearsome spirit into a small, cute, two-headed familiar who communicates freely and becomes a loyal companion. This victory establishes Mai as a Cursed Sage, a player with exceptional strategic thinking abilities that even surpass her more experienced comrades.

Throughout the story, Mai and her dependable allies, including the devoted Asagi, the cool and powerful team leader Sugiura Shinji, and the sleepy but brilliant rescuer Tango Taichi, confront increasingly difficult events within Nightmare. A major turning point occurs when Mai decides to participate in the Black Event, a high-level challenge that begins to unravel the mystery of her own past. Mai suffers from missing memories, specifically regarding her time in middle school, and she carries her mother's cryptic instruction to forget. As she delves deeper into the game, she discovers a profound connection between her lost memories and the true nature of the death game itself, leading to the revelation that her relationship with Asagi is the key to a larger, sinister conspiracy. The team must risk everything, their bodies, their memories, and their lives, to reach the endgame and uncover who is behind Nightmare before they lose themselves completely.