Among the classes included for the various characters in The Rise of Cobra include Commando, who do well at close range, Heavy Weapons, who possess extraordinary shooting skills but do it best from a distance, and Soldier, who are a balance between the two. The classic "Yo Joe!" battle cry is in the game, being used as an invulnerability power-up when the G.I. Joe character gains access to the Accelerator Armor, allowing them to be undamaged while attacking Cobra troops and vehicles.
The Nintendo DS version is a top-down arcade style shooter that re-uses assets from the finished but unreleased Gauntlet DS.
After the events of operation hiss, Duke and Scarlett travel to the Arctic and free Heavy Duty, Ripcord and Snake Eyes from the M.A.R.S Detention Center. Also, they fight the Baroness and bring her to the Pit. In Egypt, the Joes learn that Cobra is taking the Apep's Eye (Gem), and must defeat Firefly. In the jungle, the Joes discover that Cobra is making a pyramid-like (zigurat) building in the middle of the jungle. From there, the Joes must defeat James McCullen (who now takes the identity of Destro) at the rooftop of the pyramid building. Finally, they must defeat the Cobra Commander and Storm Shadow at North Magnetic Pole Volcano base.