To survive, they navigate through various environments, killing monsters and looting chests to collect items that boost their offensive and defensive capabilities.

Currency can be used to open chests found throughout the level, which drop random items; they can also be used to activate turrets and drones which assist the player.

In the metagame, players can unlock access to new playable survivors, items, abilities, and game modifiers by completing certain in-game challenges; once unlocked, new survivors and modifiers become available to select from at the start of the game, and new items will start appearing randomly from in-game chests.

Additionally, there is another currency that has a chance to drop from defeated aliens called Lunar Coins, which persists between games.

The survivors which the player can choose from in the game are Commando, Huntress, Bandit, MUL-T, Engineer, Artificer, Mercenary, Rex, Loader, Captain, and Acrid.

[2] The transition to 3D was partly inspired by fan art for the original game that showed the various objects the player collected shown on the character.

[2] Hopoo Games noted that the 3D option provided "much deeper design spaces and more possibilities for cool gameplay" as well as more ways to artistically express themselves.

[2] The sequel uses the Unity engine, which Hopoo had to learn to use, and 3D levels which the team spent a long time making.

[4] Hopoo released the game into early access on Windows on March 27, 2019; at that time they estimated that the full development process would take another year.

[5][6] During the early access period, Hopoo signed with Gearbox Publishing to release the game on Nintendo Switch, PlayStation 4, and Xbox One.

[14] The game was released out of early access for Microsoft Windows on August 11, 2020[15][16] and for Stadia on September 29 with a timed exclusive level known as Sundered Grove, which would later be added to all versions in patch 1.0.2.0.

[18] Upon its launch into early access, Hopoo Games offered Risk of Rain 2 with a "buy one, get one free" promotion for the first few days.

[28] By March 2021, the game had sold over four million units on the personal computer side alone, not accounting for console sales.