At an Antenna Company seminar, Allegra Geller (Jennifer Jason Leigh) is hailed as the "goddess of the gamepod." Armed with a single ski boot, she introduces eXistenZ, an innovative game system known as metaflesh. Enthusiastically, most attendees volunteer to experience this groundbreaking technology. Meanwhile, a game company employee named Ted (Jude Law) is tasked with screening another participant, Noel Dichter (Kris Lemche), for recording devices. Tensions rise as Noel, equipped with an outdated gamepod, grows increasingly anxious about the demonstration.
The experience begins as players interact through flesh-like gamepods. Just as they slip into a trance to enter the game, Noel brandishes a peculiar gun from his pod and shoots Allegra in the shoulder. The impact reverberates through the other players attached to her, while security swiftly neutralizes Noel. In the ensuing chaos, Ted seizes the gun and hastily takes Allegra to safety. During their escape, Allegra discards Ted's phone to prevent tracking. Ted bravely uses a pocketknife to extract the bullet, revealing it to be a tooth. They discover the gun and ammunition are fashioned from flesh and bone, evading detection by scanners.
Their journey leads them to a motel where Ted wishes to report back to Antenna, but Allegra insists on testing the game first, requiring Ted's assistance. Unfortunately, Ted is lacking a "bio-port." They visit a gas station, where they meet the attendant Gas (Willem Dafoe), who agrees to install an illegal bio-port after recognizing Allegra. However, when she connects her pod, it malfunctions, locking them out of the game. Gas suddenly returns with a shotgun, but Ted is forced to shoot him before he can harm Allegra.
Escaping once more, Allegra and Ted drive to an abandoned ski club. There, they encounter Kiri Vinokur (Iam Holm), to whom Allegra entrusts the ski boot for safekeeping. Kiri and Landry (James Kirchner) toil to repair the malfunctioning pod. Once fixed, they jack into the game, but the reality within changes dramatically as Allegra cryptically advises Ted: "You have to play the game to find out WHY you’re playing the game." They soon meet the gameshop owner D'Arcy Nader (Robert A. Silverman), where Ted realizes that non-player characters (NPCs) mirror his actions and dialogue. Nader equips them with micro-pods to facilitate their entry.
As Ted's character attempts to flirt with Allegra, the scene abruptly shifts to a trout farm where he works on a conveyor belt alongside Yevgeny Nourish (Don McKellar). The farm is now a front for manufacturing game pods and Yevgeny suggests lunch at a Chinese restaurant, recommending the special. Upon locating Allegra, Ted's anxiety escalates as he begins to question the authenticity of both the game and reality.
The pair re-enters the game, finding a disgusting dish which Ted's character consumes, only to have him reassemble the bones into the same weapon he found earlier. When he unknowingly shoots the waiter, Yevgeny reveals that the waiter was a traitor. He leads them to a breeding pool, disclosing that they are developing undetectable weapons for a secret agency. They learn that the trout farm is run by Corticle Systematics, an organization determined to eliminate non-real components like pod games.
Returning to the game shop, they find a dead Nader. Hugo Carlaw (Callum Keith Rennie) advocates for the realist underground and instructs them to kill Yevgeny. Back at the trout farm, Allegra ports into a pod, but things go awry. Ted cuts her off, only for her to bleed out in a distressing turn of events. Yevgeny arrives and sets the pod ablaze, which releases toxic spores. In a frantic moment, Allegra stabs Yevgeny, igniting a fire in the farm.
Reawakened in the ski lodge, Allegra disinfects her infected pod but soon realizes that Ted's bio-port is also compromised due to Kiri’s actions. Just as they conclude they need a break from the game, their ski lodge is stormed. The cashier from the game appears, preaching about freedom before destroying the pod. Ted realizes they are still trapped within the game.
Amidst an intense battle outside, the cashier confronts Allegra with a gun, only for Kiri to emerge and shoot him from behind. Kiri claims allegiance to Corticle Systematics and solicits Allegra's assistance, but she shoots Kiri instead. As Ted struggles with the moral implications of her actions, Allegra triggers a bomb within his bio-port, reveling in what she believes is her victorious conclusion to the game.
In a twist, Allegra and Ted wake up back at the seminar, where the audience applauds their efforts. The session proctor, Merla (Sarah Polley), announces a discount for the upcoming game, transCendenZ. The true nature of Allegra’s role as a game designer becomes evident as Yevgeny reveals his real identity. A nervous Merla discusses the anti-designer theme with Yevgeny before Ted and Allegra unexpectedly shoot both of them, proclaiming boldly: "death to transCendeZ!" As the chaos unfolds, the Chinese waiter poses a haunting question: "Are we still in the game?"
