As the amazing Spider-Man, Peter Parker has had to endure many shocks in his life: The death of his uncle Ben – shot by a burglar years ago, when Peter might have been able to stop the killing. The loss of his girlfriend, Gwen Stacy, who perished at the hands of his deadliest enemy, the Green Goblin. The realization that his wife, Mary Jane Watson, knew his secret identity years before he finally revealed it to her. But nothing could have ever prepared him for the latest unexpected turn in his life: the possibility that he has a long-lost sister!
The revelation of a sibling he didn't even know existed is far from the only complication to the matter. For not only is his sister a deadly super-villainess known as Pity, but she's working alongside the manipulative Gentleman – a man who masterminded the deaths of Peter's parents! Together with Doctor Octopus, Electro, the Vulture, and Mysterio, the Gentleman and Pity have formed the newest incarnation of The Sinister Six – a group dedicated to destroying Spider-Man!
Faced with the challenge of trying to save Pity from her predicament while, at the same time, stopping The Sinister Six from carrying out the Gentleman's world-threatening plans, Spider-Man must turn to the super-spy organization S.A.F.E. and its volatile director, Colonel Sean Morgan, for help. But even with help from his hi-tech allies, Spider-Man discovers that nothing he can do will stop the Sinister Six from achieving their goal of revenge!