The storyline of Renegade deals with the abduction of GDI's top three Tiberium research specialists by the Brotherhood of Nod. New characters include various mutants, GDI elite commandos known as the 'Dead Six' and Nod elites such as the Black hand, Sakura, and Mendoza. Nearly every unit and most of the structures featured in the original Command & Conquer has been re-created in the game, although with aesthetic changes. Also, Nod troopers looked more like their Command & Conquer equivalent, donning professional urban camouflage uniforms rather than red jumpsuits easily distinguishable on the battlefield.

The game originally featured a different commando (Logan Shephard), looking much more akin to the original Command & Conquer unit and was much less action-oriented than its final incarnation. As the game progresses it is revealed that the specialists have been forced into biochemistry research for the Brotherhood's top secret 'Project Re-Genesis', an attempt to create genetically enhanced super-soldiers with the aid of Tiberium. He conducts missions which take him all over the world in various countries and climates, both indoor and outdoor, and his actions greatly affect the current state of the war. The player assumes the role of GDI commando Captain Nick 'Havoc' Parker, who is assigned to rescue these experts. GDI's top three Tiberium research specialists have been abducted by the Brotherhood of Nod.

Renegade's story takes place during the final days of the First Tiberium War originally depicted in Command & Conquer.

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