In the near future, a renowned game designer has created an immersive virtual reality game that blurs the boundaries between reality and the gaming world. The game is accessed via a bio-organic gaming console called a "game pod," which connects to players through a "bio-port" at the base of the human spine. The console is made from mutated amphibian organs and requires careful maintenance. The designer is on the run, fearful for her life after her latest creation, a game called "eXistenZ," is targeted by "realist" groups who oppose the potentially dehumanizing effects of such games. During a focus group demonstration gone wrong, the designer is forced to flee alongside a young trainee and marketing executive.

As they evade their pursuers, the designer and her companion must play through her game to test it and ensure its integrity. They navigate a surreal landscape that challenges their perceptions of reality as they encounter various characters and tasks that seem to hide deeper meanings and purposes. The deeper they delve into the game, the more they question the reality they return to after each session, leading to a growing uncertainty about what is real and what is part of the game. The narrative weaves between these layers of existence, creating an intricate puzzle of identity, control, and intention, all while dodging potential threats from those who believe the game has gone too far.