In The Boys: This Is Going To Hurt, you battle with and or against Butcher, Hughie, Frenchie, The Female, Mother's Milk, members of The Seven, your favorite and most hated Supers, and other characters from "The Boys". You need to be fast as after 21 rounds, Homelander makes it "Game Over" for everyone.

Each round, you receive action points to spend on recruiting characters, buying additional resource or character cards, battling other players, and traveling the game board. Compound V facilitates most aspects of the game, and characters must be paid and defeated in combat to successfully recruit them. Missions are completed throughout to earn money, blackmail, and additional resources in an effort to build a team strong enough to take down Homelander.