Esta é a sequência do Loaded de 1995, com um mecanismo gráfico aprimorado e tanta violência e sangue. Re-Loaded coloca você no lugar de vários personagens, cada um estranho, deformado e geralmente estranho. É um jogo baseado em missões, onde você deve completar vários objetivos para vencer com sucesso em cada um dos 12 mundos. Ao longo de cada missão, você deve matar muitas pessoas, com uma variedade de armas, como canhões de plasma, lasers e bombas ultra.

F. U. B. , the antagonist of Loaded, had his body destroyed at the end of the previous game, although his brain fled in an escape pod. Landing on a harsh desert world, Kee-Butt-5, his brain has been implanted into the body of a chiselled, bronzed young artist hermit named Manuel Auto, and then he murdered the loyal surgeons responsible for giving him a new body. Reincarnated and renamed "C. H. E. B. ", which stands for "Charming Handsome Erudite Bastard", the former raving lunatic supervillain has taken on some of the aspects of his host body, the creative, artistic and thoughtful Manuel Auto. With his matter manipulation powers, C. H. E. B. plans to transform whole planets into "Works Of Art and Genius", starting with his own body which he grows to the size of a small moon. Once again the group of blood-thirsty anti-heroes gather to bring him down once and for all and set off for Kee-Butt-5...