At Empire State University, Peter Parker and Carlie Cooper are ambushed by Scorcher, White Rabbit and Chance, who were ordered by Jackal to attack anyone who turns up at his lab. But as the duo retaliate, they discover that the villains have spider powers too. When White Rabbit kicked Carlie in the face, Peter uses the kung fu moves that Shang-Chi taught him to defeat the villains. Though suspicious as to why he didn't do that earlier, Carlie tells Peter to call in Spider-Man, so the three of them can take down Jackal. Unknown to them, Jackal is spying on them, chuckling that it'd be impossible for both Peter and Spider-Man be in the same place without revealing his secret. He then tells Tarantula to review the tape of there fight and tells his mystery employer that phase two is about to commence.

At Project Rebirth, Venom is trying to contain Spider-King and the plague-carrying spider hatchlings he has unleashed.

Back in Manhattan, the police try to inform everyone not infected with spider-flu to head to Horizon Labs to be inoculated with the vaccine. However, many people are trying to break the quarantine, forcing the Avengers to act. This does not sit well with Major Jameson, who now hears that Manhattan is being renamed Spider-Island. He then comes in on the Horizon scientists building a spider-sense jammer to keep the infected from breaking quarantine. Mr. Fantastic then steps in to update Jameson about the source of the spider-virus. He determines that genetically-altered bed bugs have spread the infection. Though the bugs have a short lifespan, the virus they carry has mutated into an airborne strain that will turn all of humanity into a new race of Homo Arachnus. Luckily, Superhumans are immune to the effects of the virus. Unfortunately, Jameson is also infected.

In Herald Square, Anti-Venom is continually curing Spider-People of their disease. And they are none too happy about losing their powers. But Madame Web knows that not even Anti-Venom can stem the rising tide of Spider-People. From what she sees on the Web of Life, there are suppose to be only a few Spider-People at a time. And now, the future is currently uncertain.

At the 18th Precinct, Carlie finds Spider-Man, who claims that Peter has swung off to answer a call at Horizon. To prevent her from calling himself on his cellphone, Spidey informs her of a robbery in progress, headed by one of his rogues: Shocker. But when they get to the crime scene, they find that Shocker has four extra arms. Shocker insists that Spidey leave him alone, stating that he needs the money. He reveals that besides having extra arms, he has four extra eyes, and he was robbing to get enough money to pay the Mad Thinker to cure him. At the same time, Carlie starts mutating as well.

As the mutations of Homo Arachnis sprout all over Manhattan, Jackal's employer, revealed to be Adriana Soria, the Queen, declares the world her new kingdom.