River City Girls features Kyoko and Misako, two street-tough high-schoolers embarking on a mission to rescue their kidnapped boyfriends, Kunio and Riki, across the six regions of River City. Players will engage in combat using combos, counters, throws, and special attacks while battling a range of enemies. The game offers side quests, leveling up through experience points, interactions with NPCs from past River City titles, and the ability to shop for items, food, and gear to enhance stats and unlock new abilities.

Players can also utilize weapons, recruit defeated enemies to fight alongside them, and experience a mix of action-packed gameplay and RPG elements in this thrilling adventure.