The game's plot expands upon that of the film by including additional characters and elements from the Spider-Man comic books and other aspects of the Marvel Universe.

The Web-Rush bullet time mechanic from the game's predecessor also returns and has been expanded, now allowing players to also do critical strikes, dodges, and rolls.

The combat is similar to the predecessor, featuring a free flow design and counterattacks, and allows Spider-Man to incapacitate enemies for a few seconds by various means, such as throwing interactable objects at them, and then subdue them for good by webbing them.

The game's map has been expanded compared to its predecessor, and now also features a subway system that allows the player to travel to Peter Parker's home in Queens, which serves as a hub.

From where, players can replay story missions and equip alternate costumes for Spider-Man, unlocked from investigating Russian Hideouts or via DLC.

Peter Parker has been fighting crime in New York City as Spider-Man for a year, motivated by the death of his Uncle Ben at the hand of criminal Dennis Carradine.

Later, Spider-Man stops Schultz's gang and the Russian Mob from destroying the Oscorp building while raiding it for advanced weapons to help them win the turf war they have engaged in.

Spider-Man rescues an electric engineer named Max Dillon, who idolizes him, and defeats Schultz, who is calling himself the "Shocker" after stealing a pair of vibro-shock gauntlets.

Fisk intends to take over Oscorp however, albeit patiently, waiting for Harry to slowly die from the disease that killed his father, Norman Osborn.

Spider-Man begins to be mentored by Kraven the Hunter, who teaches him his hunting techniques to help him become a better hero, while working together to track down the Carnage Killer.

Revealing his real name is Cletus Kasady, the Carnage Killer claims that he and Spider-Man are very alike and should join forces, but is promptly defeated and arrested.

Kasady is taken to the Ravencroft Institute for the Criminally Insane, where he is experimented on with a red substance code-named "Venom", originally meant to cure Norman Osborn's illness.

The Kingpin sends Felicia Hardy, a former bank robber who gained super-powers through genetic experiments funded by him, to kill Spider-Man, but she refuses to do so.

Harry asks for Spider-Man's blood, believing it can be used to develop a cure, but the hero, afraid of the possible side effects, refuses to give it to him without properly researching it first.

Later, while responding to an attack on Oscorp, Spider-Man is shocked to find Harry, who has become the "Green Goblin" after injecting himself with Richard Parker's spider venom in hopes of curing himself.

Beenox originally planned to develop the 3DS version of the game, but dropped due to unknown reasons and was given to High Voltage Software instead.

Whitehead stated: "Sullied by lacklustre gameplay and trampled by technical shoddiness, this time Spidey hasn't been done in by the Sinister Six, but reduced to a Terrible Two".

[26] By November 2015, Beenox had lost its license to develop console Spider-Man games, being restructured as a support studio within Activision for their Skylanders and Call of Duty franchises.

[27] The digital version of The Amazing Spider-Man 2 was delisted alongside the first game on January 4, 2017 across Steam, Xbox, PlayStation and Nintendo platforms.