The Spider-Tracer killings have had a large political impact and mayoral candidates Bill Hollister and Randall Crowne are both determined to stop the murders in any way possible because the general public will back-up whoever does so. In any case, the general public is against Spider-Man and since Hollister is fully supporting the local police, his hope in winning the election lies in Spider-Man's capture, and the police are determined to take him down.
While attempting to escape from the police trailing him, Spider-Man is shot in the shoulder by a police marksman and although seriously injured, he manages to escape by crawling up an elevator shaft.
Meanwhile, NYPD crime scene investigator Carlie Cooper is given by her colleague at the department an electronic device that allows her to track down the Spider-Tracers that are found on the victims' bodies, hoping to lead her to the actual murderer.
Also, at Liberty Island, Harry Osborn proposes to his girlfriend Lily Hollister but Lily remains undecided and after receiving a call from her father, leaves Harry heartbroken and in the shadow of his Goblin past.
A bleeding and wounded Spider-Man manages to get to his appartment and enters the bathroom unseen just when a police officer comes in to inform Peter's roomate, police officer Vin Gonzales of something urgent. Then on, Carlie's tracking device leads her to Vin and Peter's appartment where she finds a bag full of spider-tracers under Vin's bed. Carlie confronts Vin about being the Spider-Tracer killer, and while they were talking, Peter overhears them mentioning that the Goblin villain known as Menace is attacking a Hollister Rally so, despite being injured, he donnes his costume and goes to fight Menace. However, because of his weakened state, Spider-Man is no match for the villain and he is badly beaten and left for the police who finally arrest him.
Menace then goes to the Hollister Headquaters where he starts experiencing some sorts of transformation, reverts to his alter-ego: Lily Hollister. While in this form, Harry enters the room and is shocked to discover that his girlfriend is Menace. It is revealed that Lily discovered of Harry's and his father's pasts as the Green Goblin while going through Harry's journals thinking he was using drugs. In an attempt to expose Norman as the Goblin so that her father would be seen as a hero and launch his career in politics, Lily goes to Oscorp for proof of Norman being the villain but while she was in Norman's secret lair, she was accidentally exposed to a new form of Goblin serum that Norman was working on, giving her super strength and the ability to shape-shift from her normal form to that of a Goblin at will. Lily also reveals that she was attacking her father's campaigne hoping he would gain public sympathy and a boost in votes. Also, she left Spider-Man to be arrested by the cops because it would increase Bill's chances of winning the election. Harry was shocked at the numerous revelations made by Lily, and was given yet another shock when Lily accepted his proposal,
Spider-Man is taken to the NYPD precinct and after he refuses to co-operate, Palone, the interrogator attempts to take his mask but he is stopped when Matt Murdock enters the precinct and declares that he will represent Spider-Man in court.
Carlie goes to the precinct and tells Palone of Vin's involvement in the Spider-Tracer killings. Then, Palone calls Vin and tells him that a warrant is issued for his and Carlie's arrest. Then Vin's partner arrests Vin for criminal conspiracy and takes him to the same prison Spider-Man is being kept in. Vin is put in general population with other violent inmates and Spider-Man fears for Vin's safety and tells Matt that the circumstances have changed.
On Election Day, at the trial, Spider-Man pleads not guilty and derails the trial. Matt then hands him a law book that contains a web-shooter he took from the evidence room. On Riker's Island, Vin is being brutally attacked by the other inmates in General Population until Spider-Man appears and saves him. They escape together and Vin tells Spider-Man about the Spider-Tracer conspiracy. Meanwhile, a terrified Carlie goes to the Hollisters' headquarters and tells Lily and her father that the NYPD is after her for a crime she did not commit. Bill and Lily are determined to help Carlie in any way because they consider her a part of their family and when the cops burst in, Lily secretly changes into Menace and attacks the cops to protect her best friend.
When Spider-Man hears of Menace's attack he quickly goes to stop her but because he is still in a weakened state, Spider-Man is defeated yet again. Before the killing blow is delivered to Spider-Man, Harry Osborn, wearing a Green Goblin costume and using a Goblin Glider appears and attempts to inject Menace with a special syringe but she manages to grab it. When the Green Goblin calls Menace Lily, Peter realizes that the two Goblins in front of him are Harry and Lily so he takes the syringe and injects Lily with it in the neck, causing her to transform back to her human form. She is then arrested by thepolice and Spider-Man is brought to the safety of a rooftop by Harry.
The whole encounter was shown on television and upon discovering that his own daughter is a criminal, a distraught Bill Hollister, despite being declared the winner of the election, resigns from his post as Mayor. Vin meets up with Carlie and tells her that he will fix things for both of them and goes to arrest the cops involved in the Spider-Tracer conspiracy.
In the Epilogue, Peter and Harry talk about Lily at the Coffe Bean and Harry wonders what he will do now that Lily is insane because despite everything he really loved her. Elsewhere Lily is visited by Norman Osborn who consoles her and welcomes her to the Osborn Family.