The Punisher arrives at the prison on Ryker's Island. He is watched by every prisoner, and also by the warden Gerty and his aid, who both talk about the possibility to use the Punisher in their plans (which we do not know still).

After smashing down his cell's partner, the Mule, the Punisher starts investigating who might have poisoned him in his past time in prison. He correctly deduces that the cook is the only one who would have been able to manage to get poison into his body. He tips off the cook that he knows it was him which spooks the cook, causing him to run to the guy who gave the order to poison the Punisher: Jigsaw.

They fight and the Punisher crashes a bottle in Jigsaw's hand, but then Don Cervello enters and stops the fight. Cervello is the boss among the prisoners and he also has some guards in his pocket. The Punisher figures out there is an escape in progress and makes Cervello include him in the pack of escaping prisoners.

But the following days the Punisher sees that Cervello has other plans for him and suspects Cervello is planning his death. The night of the escape arrives and Cervello sends Gregario, one of his men, to kill the Punisher. But the latter simulates his death and follows them.

The Punisher could escape alone, but decides to stay and stop all the prisoners escaping before they get out of the prison and endanger innocent people in NY. So he assaults a security tower, shoots down Gregario and avoids the escape.

Only Jigsaw and Cervello keep running, kill a guard, and arrive at the warden's office.

The Punisher gets to the warden's office, too. Jigsaw threatens to kill the warden and his aide unless the Punisher surrenders his weapon. The Punisher puts a bullet that is too big for the gun in the chamber and throws it to Jigsaw, who fires it, exploding the gun and injuring himself. Cervello threatens the warden, but the Punisher does not care about the warden's life, so Cervello surrenders and is caught by the arriving police officers.

Then the warden tells the officers to leave the Punisher with him, and tells the Punisher about the Trust, a secret organization of industrialists, financiers, ex-military, movie stars, journalists and more, who want to fight criminals with methods beyond the law, like the Punisher himself. The Punisher agrees to work for the Trust to get his equipment back and get out of prison.

In the end, the gangster boss Charlie Siciliano meets his nephew Tony Massera, the son of a gangster killed by the Punisher some months ago and hands him a gun to kill the Punisher himself.