The player is a new S.H.I.E.L.D. recruit, dispatched by Nick Fury and Maria Hill, as an unknown event, referred as "The Pulse" causes a strange material known as Iso-8 to emerge on Earth. The material has various properties, but is primarily used in the game to power up characters. The player is charged with joining various heroes in battle to take down numerous villains who are all aiming to gather and use Is-8 for their own nefarious purposes. As the game advances, more heroes join the conflict as playable characters. The game had 2 seasons; Season 1 was an original plot where Hydra was eventually revealed to be using Iso-8 to resurrect Red Skull, which results in Magneto turning over to fight alongside S.H.I.E.L.D.; Many other villains would follow suit. Season 2 was heavily inspired by the Fear Itself story-line but also contained other details such as Incursions as part of Time Runs Out, that would eventually lead into Secret Wars. Season 2 ended with the defeat of the Serpent, at the cost of the lives of Thor and Jane Foster (as Mighty Thor, who arrived via Incursion).

The player is a new S.H.I.E.L.D. recruit, dispatched by Nick Fury and Maria Hill, as an unknown event, referred as "The Pulse" causes a strange material known as Iso-8 to emerge on Earth. The material has various properties, but is primarily used in the game to power up characters. The player is charged with joining various heroes in battle to take down numerous villains who are all aiming to gather and use Is-8 for their own nefarious purposes. As the game advances, more heroes join the conflict as playable characters. The game had 2 seasons; Season 1 was an original plot where Hydra was eventually revealed to be using Iso-8 to resurrect Red Skull, which results in Magneto turning over to fight alongside S.H.I.E.L.D.; Many other villains would follow suit. Season 2 was heavily inspired by the Fear Itself story-line but also contained other details such as Incursions as part of Time Runs Out, that would eventually lead into Secret Wars. Season 2 ended with the defeat of the Serpent, at the cost of the lives of Thor and Jane Foster (as Mighty Thor, who arrived via Incursion).