FusionFall features more than a thousand items the player can collect. Items are divided into four main types: weapons, armor, accessories, and vehicles. Weapons and armor modify the player's attack and defense, while accessories are used for decorative purposes. Vehicles allow the player to move around faster. Items are generally found inside C.R.A.T.E.S., which can be obtained by defeating Fusion monsters, completing Missions, or winning races inside Infected Zones. Some missions also give specific items, and a wide array of items can be bought from NPC Shopkeepers.

Items come in four types of rarity: common, uncommon, rare, and ultra-rare. In the case of weapons and armor, each type is progressively stronger than the previous type, while accessories have no such distinction. The rarity also determines how much the item can be sold for at a shop to a shopkeeper. A few items are not able to be sold Numbuh One's glasses and all vehicles. Upon selling an item the player recieves a small compensation for the item. Selling price can be seen when the item is clicked on in the inventory screen. Items can only be equipped if the player is equal to or at a higher level than the item. Rarity does not affect the ability of a character to use the item. Certain items are also restricted to specific genders. 

Weapons modify the player's Attack stats: single and group. Players can equip two weapons at time and switch between them. Pistols and rifles provide a larger single attack but a smaller group attack, making them more effective against enemies which travel alone. They can only target one enemy at a time. Melee weapons and shatterguns provide a larger group attack but a smaller single attack, making them more effective against enemies which travel in packs. They can target up to three enemies at a time. Thrown weapons and rockets provide an even larger group attack than melee weapons and shatterguns, but likewise provide a smaller single attack. In addition, both weapons have to be aimed manually. All enemies within the splash radius of the explosion are harmed by the attack.

Armor adds to the player's Defense stat. Only one of each can be used at any given time, but their combined Defense values are added to the player's.

Accessories are decorative items which do not affect combat. One of each may be equipped at one time. Certain types of hats will prevent any equipped glasses from appearing, but backpacks will always be visible.

Vehicles are an alternate mode of transportation which allow the player to travel at roughly the same speed as they would with the Run boost active. When using a vehicle, players cannot use Nanos, engage in combat, click on other characters (NPC or player), or use emotes. Vehicles also won't work in Infected Zones. However, all vehicles hover above the ground, protecting the player from toxic Fusion Matter. Vehicles have a rental period of 7 or 15 days (depending on the version of the game), after which they must be rented again.

Items in these categories are obtainable through special means.

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