The basic gameplay of Dungeon Hunter 5 shares some similarities to its predecessor, Dungeon Hunter 4, such as picking up loot, using skill attacks and using potions. However, unlike its predecessor, the game is not an open-world nor exploration, but rather a level-based dungeons that have a series of difficulties. As players progress, they will encounter progressively enemies to test their skills. Dungeon Hunter 5 does not contain a class system; instead players choose a starter type of weapon in the beginning in the game. The player character can also add friends though they can no longer co-op in missions. There is also an energy system which restricts the players from performing too many dungeons.
Aside from these main features, there is also a new mode called Stronghold in which player characters can collect minions to place them inside the stronghold. A new type of currency called quartz can be used for fusing minions. If a player fights and raids another player, their shield will switch off, thus making them vulnerable to attacks from other players. This has a level up ranks which forces the players to fight even more powerful players across their strongholds. There is also a trophy system in which players can gain trophies by winning, but it can decrease if they lose the raid attempt.
The loot system has also been expanded, not just the melee weapons, ranged weapons and armor body parts, but also the evolution items, skill weapons, backpacks and belts. A new fusion system has also been implemented in which players can pick an item and fuse it with unequipped or unwanted ones. Prior to the loot and fusion system, there is an evolution system where the item's level is maxed out, the player can use evolution materials to evolve them.