Monster Hunter Stories features a completely new gameplay structure compared to the previous titles in the series. The player assumes the role of a Rider who befriends monsters by stealing eggs and hatching them. The player then has the ability to name their companion monsters, or "Monsties", ride them around in the overworld, and have them join the player in battles.[7][6][3] The player will be able to explore different environments, encounter monsters in the field, battle them, collect items and steal eggs from monsters' nests.

Unlike most games in the franchise, Monster Hunter Stories features a more traditional turn-based battle system. During the player's turn, both the rider and their monsters will get to attack the enemy. Attacks for both the player and the enemy come in three types: Power, Speed, and Technical. Each category is stronger against one in particular in a rock-paper-scissors fashion: Power will win against Technical, Technical will win against Speed, and Speed will win against Power. When an enemy monster is targeting someone and that character attempts to attack them, a Head-to-Head will occur which pits their two attack types against each other, with the dominant attack type prevailing in the exchange. If the player and their monster both use the same attack type while the enemy is targeting someone and have the type advantage, they will unleash a Double Attack and prevent the enemy from retaliating altogether. Winning battles will award the player with experience points and item drops. Beyond the main story, the player can engage in sidequests, called subquests, which provide item and experience rewards upon completion.

In this game, the player only has a choice of four weapons from the core series to use in battle, those being the Great Sword, the Sword & Shield, the Hammer, and the Hunting Horn. The player will have access to different skills depending on the weapon and equipment they use, and the player will also be able to use items in battle.[3][16] Companion monsters can be customized with the Rite of Channeling feature, in which the player can transfer Bond Genes into a monster's slots in order to unlock and awaken their stats and abilities. This allows for further customization and adjustment to the player's play style.[8][3] The game features multiplayer battles via local or Internet connection.[17][8] The Nintendo 3DS version is also compatible with Amiibo figures, with the figures from the Monster Hunter Stories line of Amiibo unlocking original and special monsters, among other bonuses.[3]