Action Hotline Miami 2: Wrong Number takes the user to 1985, when the active phase of the war between the USA and the USSR begins. After the conclusion of the peace treaty, the Russian mafia penetrates into all areas of life in the United States. The Ghost Wolves squad decides to challenge these mafiosi. The gameplay is an almost constant stream of violence, shootings, murders and bloodshed. The user has various options for destroying enemies. The main character can control various characters. Each of them has their own history, character and abilities.

Hotline Miami 2: Wrong Number has the following playable characters:

• Alex and Ash. Brother and sister, always acting in pairs. They have swan masks;
• Butcher – Martin Brown. Adapted from Jacket for the horror film The Midnight Beast;
• Fans. A gang of killers trying to take Jacket as a role model;
• Tony. Wears a mask of a wounded tiger;
• Mark. Wears a bear mask;
• Corey. The girl who wears a zebra mask;
• Manny Pardo. A detective who investigates crimes and at the same time uses lynching;
• Evan Wright. A writer who became interested in Jacket's story. Wants to write a book about it;
• Jake. An overweight man with many snake masks;
• Richter. Has a rat mask;
• Henchman. Representative of the Russian mafia;
• Son. Leader of the Russian mafia;
• Soldier. His name is Nikki, and he is Jacket's co-worker.

The main character is given tasks by members of various gangs. All these tasks are united by one common motive. This is violence. The game features constant clashes against the mafia. However, they always outnumber the Phantom Wolves team. With each new level, new options for destroying and executing opponents open up for the protagonist.