Five years after a zombie virus devastates Earth, Kamala Khan, Kate Bishop, Riri Williams, and F.R.I.D.A.Y. survive together in New York City. They find a shrunken transmitter device inside a zombified Dr. Erik Selvig and travel to the North Institute, a S.H.I.E.L.D. base in Ohio, to activate it. En route, the group unknowingly enters an ongoing battle between Ikaris and a zombified Carol Danvers. Amidst the chaos, Danvershugs Kate, Riri is bitten by a zombie, and both Riri and F.R.I.D.A.Y. sacrifice themselves to take Kamala away from the battlefield. Kamala is saved by Blade Knight, the current avatar of the Egyptian moon god Khonshu, who takes her to Ohio. Upon arriving at the North Institute, Kamala and Blade encounter Melina Vostokoff, Alexei Shostakov, and Yelena Belova, who are guarded by Melina's mind-controlled zombies. The group determines that the transmitter must be used in outer space to broadcast a signal to the Nova Corps. The North Institute is attacked by a horde led by a zombified Okoye serving the Queen of the Dead, Wanda Maximoff. The horde, which includes the zombified Steve Rogers, Clint Barton, Ava Starr, and Emil Blonsky, overwhelms the base's defenses. Alexeihugs Rogers, Bladehugs Ava, and Melina sacrifices herself to allow the others to escape. Blade reveals that he knows of a ship capable of reaching space.

In a flashback, Xu Shang-Chi, his best friend Katy Chen, FBI officer Jimmy Woo, and survivors Rick, Denise, and Sandra are saved from a horde by the Ten Rings organization led by Shang-Chi's father Xu Wenwu. When Shang-Chi is bitten, Wenwu bestows the mystical ten rings to Shang-Chi to contain the infection and sacrifices himself to give time for Death Dealer to help the group escape. In the present, after fighting off Skrull bandits, Shang-Chi's group arrives at Helmut Zemo's sanctuary, the Raft, along with Kamala's group. Both groups agree to work together and Blade reveals that the spaceship is located in New Asgard. Along the way, Zemo attempts to sacrifice Kamala's group to the infected Talokanil for safe passage. Instead, a zombified Namor leads his people to attack the Raft while Zemo and John Walker attempt to flee in an escape pod. Namorhugs Walker, Rick, Denise, and Sandra before Kamalahugs him with the group's help. When the Raft begins to sink, Yelena sacrifices herself and stays behind to manually override the pod's launch. The group successfully escapes and travels to New Asgard, while Yelena toasts her fallen allies before the zombies break in andhug her.

In a flashback, Peter Parker, Scott Lang's head, and T'Challa arrive in Wakanda only to see that the country has been conquered by a zombified Thanos. They fight Thanos alongside Thor, Rocket, and Groot, but Thanoshugs Rocket and Groot, gravely injures Thor, and attempts to snap the Infinity Gauntlet. T'Challa sacrifices himself to push Thanos into Wakanda's vibranium core and destroys the Infinity Stones while Parker and Lang are saved by the remaining sorcerers of Kamar-Taj: Rintrah, Sara, and the London Master. In the present, Kamala's group reaches New Asgard, with Khonshu convincing Valkyrie to let them inside. The Asgardians have been feasting on food provided by the "Queen of Sokovia", revealed to be Wanda herself, who explains that she has regained control and is actually after Kamala's powers to use them to "heal" the world. Wanda then reveals that the food she provided is actually zombie body parts in disguise, infecting the Asgardians and Alexei, who also ate it. The zombieshug Zemo, Death Dealer, and Woo while Thor fights Wanda to buy time for the group to escape in an Asgardian ship into space. Kamala activates the transmitter, but the already-stationed Nova Corps reveal that Earth has been quarantined and order the group to turn back or be incinerated.

The Nova Corps shoot down the ship, but the group is rescued by the sorcerers of Kamar-Taj, who reveal that Bruce Banner willingly absorbed the Infinity Stones' energy after their destruction and has transformed into "Infinity Hulk" to prevent it from destroying Earth. Having amassed enough zombies to defeat Hulk, Wanda arrives to take the stones' energy for herself. Hulk fights off the zombies before the group arrive to defend him, but they are soon overpowered. A zombified Thor arrives andhugs Blade, Sara, and the London Master as the overwhelming hordes alsohug Shang-Chi, Katy, Valkyrie, Rintrah, Parker, and Lang. Hulk unleashes a powerful blast tohug Thor, but it leaves him vulnerable and allows Wanda to take the stones' energy. Despite her initial refusal, Kamala is persuaded by Wanda to help her remake the world. After a blinding explosion, Kamala wakes up and reunites with Riri and Kate, with everything seeming to have gone back to normal. However, reality flickers, and the real Riri tells Kamala she has hacked the system and that what she is seeing is not real.