Captain America is airdropped into Central Park, where Venom is already fighting the Queen. The Queen gets the better of him but he is saved when Venom stabs her in the back with Cap’s shield.

She appears to be dead but instead transforms into a giant spider. Regardless, Cap and Venom stand ready to fight.

In Horizon Labs’ Lab Six, Spider-Man and Kaine hear people approaching. They quickly change clothes because Kaine’s longer hair does not resemble Peter’s.

Before Reed, Max Modell, Grady, and Bella can investigate Lab Six, the alarm goes off. When they check to see what the problem is, they find Mary Jane with the people who she saved at Our Lady of Saints Church. Mary Jane asks why she is only in stage two of the virus and is told it’s from all the years she was “with” Peter.

They go to Lab Six and find Peter Parker in his underwear and Kaine dressed as Spider-Man. Peter and Kaine then go to Peter’s lab, where Peter changes back into Spider-Man and gives Kaine his stealth suit, which is impervious to the Queen’s sonic scream.

Meanwhile, Cap and Venom are leading the Queen to Union Square and sends out a message to the other heroes to assemble there. Along the way, Spider-Man and Kaine run into Madame Web, who tells them that the Queen is feeding off the Web of Life and is drawing her strength from the enslaved spider monsters. The only person who can stop her is Spider-Man, but that means he would have to kill her, something he isn’t willing to do. They catch up and join the fight, during which Mary Jane and the other heroes arrive.

Spider-Man is discouraged by the fact that everyone else has his powers, which makes him like everyone else, but Mary Jane gives him a pep talk and tells him to try and build something. He then realizes that the spider-slayers Smythe was talking about were Doc Octopus’ Octobots he and Carlie found while they were digging through confiscated weapons at the 18th Precinct. All they need now is an antenna that can cover all of Manhattan.

In Union Square, the Avengers, X-Men, and Young Allies prepare for the last stand of Spider-Island. Madame Web believes it is hopeless but Shang-Chi arrives with the Immortal Weapons, something she did not foresee.

Mary Jane leads Spider-Man to the Empire State Building, where they hook up the control panel for the Octobots. Spider-Man puts it on and sends the Octobots to Horizon Labs to distribute the cure.

Back in Union Square, the heroes are overwhelmed by the Queen and her spider horde when the Octobots arrive and begin to cure all the spiders. Because of this she starts to weaken.

At the Empire State Building, Mary Jane tries to hold off the spiders that are trying to stop Spider-Man. When he realizes that he’s saving the day, Mary Jane whispers, “I love you,” which he doesn’t hear.

As the Queen continues to lose strength, Ms. Marvel and Kaine perform a move she and Spider-Man practiced where she throws Kaine towards the Queen’s head. Madame Web realizes that she read her prophecy wrong; Kaine is the one who’s supposed to kill the Queen. The Queen tries to use her sonic scream on him, but the stealth suit protects him from it as he tears threw her head. The heroes then all attack at once to make sure she’s dead.

In the end, they manage to kill the Queen, and Spider-Man and Mary Jane, still atop the Empire State Building, sit together, staring down at the cured New Yorkers.