After the fall of mankind, only one survivor walks the streets of New York. His name is Frank Castle and he is the last gun on earth!
"Patient Zero" is playing a game of cat and mouse with him, as is his messenger, the infected and insane (more than usually) Deadpool. It seems that there are still survivors and as Frank is out to destroy all mutant cannibals and doing better now than ever since there is no law to stop him, Patient Zero wants to make him an offer he can't refuse.
Upon rescuing a Priest and a young boy, it becomes fact that human survivors may still exist, only Frank is done with playing heroics, and taking spiritual advice from the church.
But when he is forced into a stalemate by the further mutated but still coherent Spider-Man, who is out to rescue Mary Jane from the dominant tribe of New York, there is no way out but death and maybe the chance to take as many of his enemies down with him... unless he truly does have allies in his new-found nemesis!
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