After the fierce battle to stamp out the nefarious drug SEED, resurrected gunman Beyond the Grave (Grave, for short) resumed his slumber, with Mika Asagi watching over him. Yet even with the defeat of Garino Corsione's criminal organization, the distribution of SEED continued, and Mika set about hunting down all traces of it across the world.

After 14 years, Mika tracked the manufacture of SEED to South City, which was in the grips of a wave of new infections. The appearance of new Orgmen—monsters transformed by the drug—turned the city into a battlefield. Mika remembered the faces of all those she had lost in the fight against evil—especially those of her father, Big Daddy, and mother, Maria—and resolved to set up base in South City.

"Lend me your power, Beyond the Grave!” Clad in black and wielding his set of dual guns, Cerberus, Grave will take to the streets to defeat a new group of Orgmen and stop the flow of SEED once and for all.