He soon arrives in Zola's special lab, where he prevents Zola from giving the Red Skull a perfected Super-Soldier Serum and defeats Iron Cross. Learning that Hydra's leader, the Red Skull, is arriving to see Zola's work and bringing the Cosmic Cube with him, Captain America decides to pursue him instead. He eventually reaches and fights her, though she escapes.

While Bucky rescues the POW's, Captain America rescues Dugan before pursuing Madame Hydra, who has taken Falsworth. After escaping his cell and while making his way through the complex, Captain America rescues Bucky Barnes, who informs him that Dum Dum Dugan and James Falsworth, among other POW's, are being held captive nearby. Abraham Erskine's Super-Soldier Serum and captured some of the Invaders before imprisoning Captain America. The former awakens in Zola's lab, with Iron Cross and Madame Hydra restraining him as Zola explains how he drew samples of the Captain's blood to recreate Dr. Making his way through Hydra forces, Captain America fights Baron Wolfgang Von Strucker, who manages to knock him unconscious. Captain America drops down in a village near a Bavarian castle and disables the anti-air cannons so the Invaders can enter the village before proceeding to destroy a nearby armory to prevent the Nazis from receiving more weapons. Arnim Zola's Project: Master Man, which involves unlocking the human genome's secrets and achieving immortality. While in communication with Peggy Carter, Captain America learns that the munitions recovered from the battle came from the Bavarian mountains based on the rare metal used and is briefed on HYDRA scientist Dr. soldiers are attacked by HYDRA, but Captain America arrives to save them and fends off the Hydra forces before contacting Howard Stark with regards to the enemy weapons. All Captain America: Super Soldier gameplay and cinematics have S3D support. It uses TriOviz for Game Technology, which is integrated with Unreal Engine 3, for stereoscopic 3D support. The Xbox 360 and PlayStation 3 versions of Captain America: Super Soldier include a stereoscopic 3D mode for 3D HDTVs and for 2D HDTVs via Inficolor 3D glasses.

Intel points can be collected by beating soldiers or retrieving items on the battlefield. The controllable character can be upgraded through Intel points. Captain America can also deploy a Tactical Vision that reveal the position of interactable surfaces.

The character can use a variety of shield attacks that can be used to defeat enemies, solving puzzles, and climbing up walls. Captain America: Super Soldier combines a combat system inspired by the Batman: Arkham series with platforming elements.

Captain america super soldier demo