Two new gameplay modes have been introduced since the original Mortal Kombat 3: the 2-on-2 mode which was similar to an Endurance match but with as many as three human players in a given round on both sides (these had not been seen in the series since the first Mortal Kombat), and a new eight-player Tournament mode. An extra Master difficulty is present. Shao Kahn's Lost Treasures – selectable prizes, of which some are extra fights and others lead to various cutscenes or other things – are introduced after either the main game or the eight-player Tournament are completed.

To balance the gameplay, some characters were given new moves and some existing moves were altered. Some characters were given extra combos and some combos were made to cause less damage. Chain combos could be started by using a jump punch (vertical or angled) or a vertical jump kick, which creates more opportunities to use combos. Combos that knock opponents in the air no longer send one's opponent to the level above in multi-layered levels; only regular uppercuts do this.