The game is set from 1943 to 1957 in Empire Bay (the name is a reference to New York's state nickname "The Empire State"), a fictional city based on San Francisco and New York City, with influences from Chicago and Detroit. The game will feature a completely open-ended game map of 10 square miles. No restrictions are included from the start of the game.There will also be around 50 vehicles in the game, as well as licensed music from the era.

Many firearms from the previous game will make a return. For example the Thompson submachine gun, the Colt 1911 and a pump-action shotgun. As seen in screenshots, new WWII-era weapons like the MP 40, the M3 submachine gun, and the Beretta Model 38 will make an appearance in the game as well as the MG 42.

Interacting with objects in the environment involves two action buttons- a standard action and a "violent" action (for example, when stealing a car, the player may choose to either pick its lock or break the window glass), used in context-sensitive situations. A map will be included as in the original Mafia game. The checkpoint system has been completely overhauled. New controls include a cover system that allows the player to hide behind objects (such as generators, walls and large crates) to shoot enemies, rather than just using a crouch while behind an object. Flanking may be a large part of the combat.

It has been stated by 2K Czech that the game's cutscenes are created by the game engine, in real-time, rather than pre-rendered cutscenes.