The Cobras numbers five members: Blood, Hawk, Boomer, Sledge and Kate, the damsel in distress, described as Hawk's protegee and wearing a blue shirt similar to his. One day, Kate is kidnapped by the Dead End Gang under the leadership of Faust, who is looking for the leadership of all street gangs in an attempt to take full control of the city. The four men go to enemy territory to save Kate, fighting through the waves of enemies that are sent against them.

The game uses 'punch' and 'kick' buttons rather than 'jump' and 'attack'. The special punch-plus-kick attack is the only aerial attack. Every time this special attack is performed, it takes away one bar of energy from the character. The players can also use different weapons that belong enemies or are hidden inside boxes, like a shotgun (with limited cartridges), baseball bats, knives and bottles.

After defeating the Big Boss at the end of the chapters, the game doesn't end: first it resuscitates all the bosses in a massive final fight, and if the player defeats them all, then Vendetta's story starts from the beginning, with an amped-up level difficulty.