The story features many old Spider-Man villains: Sandman, Electro, Chameleon, Mysterio, Hammerhead, Lizard, Morbius, the Living Vampire and Rhino[2][3] as well as appearances by Deadpool,[4] Scorpion II, Vulture (Jimmy Natale), and Juggernaut.

The fact that it's so relentless and that these battles and fights build throughout several months is going to have a cost for Peter Parker, and perhaps someone is going to take advantage of that.A revamped Doctor Octopus temporarily takes over New York City as Ana Kravinoff captures Madame Web.

Seeing that Dexter Bennett has secured a bailout from the federal government to save the Daily Bugle, he starts a public and social media movement to turn the people of New York against Dexter Bennett and the New York Stock Exchange for their greed.

Electro has been offered a very expensive cure for his declining health by the Mad Thinker, but is unable to pay for it.

To get the money for the cure, he makes a deal with Dexter Bennett in exchange for calling off the campaign against him.

The Mad Thinker attempts to cure Electro, turning him into an artificial electrical thunderbolt, but Spider-Man intervenes.

Spider-Man eventually defeats him, but not before Bennett is crippled by falling debris and the Daily Bugle is destroyed.

[10] Spider-Man helps Carlie Cooper with an investigation involving three murders and a missing girl named Keemia Alvarado.

Meanwhile, Peter begins working full-time at the Front Line and on his first story the new Rhino attacks Aleksei.

"[13] Black Cat helps Spider-Man to steal the vial of Peter's blood that Mister Negative has and replaces it with a vial of pig blood, so Mister Negative is unaware of losing the ability to kill Spider-Man through his Devil's Breath formula.

[14] Spider-Man discovers that Morbius was behind the theft of his blood and was using to it to try to find a cure for the zombie virus that has infected Jack Russell.

In the issue, there is also a side-story "The Five Stages of Grief" written by The Spectacular Spider-Man TV series co-creator Greg Weisman.

It shows Flash Thompson dealing with the five stages of grief for losing his legs[15] during the Iraq War.

The mob starts pulling up fake claims that Jameson had created the new Vulture and the media gets a hold of it.

However, Jameson reveals that the photo is a fake and fires Peter in public, who ends up running out of City Hall.

Aleksei and his wife try to go into hiding in protective custody, but the new Rhino attacks the vehicle taking them to a safehouse and Oksana is killed.

Meanwhile, Michelle Gonzalez arrives to the ensuing fight to stop the man she was defending in court to ruin his second chance.

Then an explosion is heard outside and Peter sees Arachne fighting Ana and Alyosha Kravinoff, so he rushes to help her.

After a battle with them, they go to Mattie Franklin's apartment where they find Ezekiel Sims, a wall-crawling superhuman who had died prior to these events.

Peter finds a coffin with Kaine's corpse along with his black suit with a note from Kraven reading "Hunt Me".

Due to the visions that Arachne received, Spider-Man reluctantly lets Kraven live and states that his return gave him a second chance and he should use it.

In the Savage Land, Kraven decides to hunt his own family where if they survive long enough, they could be called a Kravinoff.

He breaks Sasha's neck for arguing back and euthanizes Vladimir due to respect for the dead.

Alyosha then leaves, but Ana then makes a deal with Kraven: if she kills her brother, he will train her and create a stronger family.