Unlike in Thing-Thing 2, where you have to get to the end of the level and killing some enemies along the way, Thing-Thing Arena has you going up against endless waves of enemies in an enclosed area. It features four gameplay modes;
- Survival Mode: It has returned from Thing-Thing 2, and this time, you have to fight off as many enemies as you can before you die. But this time, the enemies are armed with guns and can fire at you, and the difficulty progresses as your number of kills grow.
- Zombie Survival: A new twist on Survival Mode, where you face zombified enemies that move faster and drop less health pick-ups. You also start with less health, as well, but don't worry, you'll have a nigh-infinite supply of ammo in your "Zombie Special" (a Franchi SPAS-12 shotgun).
- Super Survival: A tougher version of the standard Survival Mode, where the enemies come with stronger weapons. In addition, your starting loadout also comes with a Gyrojet with 20 rockets and a Milkor MGL with 30 grenades.
- Stinky Bean Survival: The game also marks the first appearance of the "world's most pathetic lifeform", the Stinky Bean. Even though they're not armed with guns, they're still a threat in numbers.
- 1911 Custom: The famous M1911 .45 ACP handgun designed by John Browning returns, this time with a laser sight attached to it.
- Walther P99: A handgun designed in Ulm, Germany by Walther arms in production since 1997. Has less recoil than the 1911 Custom. Features a laser sight mounted beneath the barrel.
- Beretta 92FS Silenced: A variation of the Italian handgun produced by Beretta since the 1970's. Chambered for 9x19mm Parabellum rounds, and comes equipped with a laser sight and a silencer for quieter shots. The silencer adds to the barrel's length, so if an enemy is close enough to you and you fire the weapon, you wouldn't be able to hit him.
- Heckler & Koch VP70: The world's first polymer frame handgun manufactured from 1970 to 1989 by Heckler & Koch, chambered for 9x19mm Parabellum rounds. The variant featured in the game is the select-fire VP70M (military), and has the shoulder stock equipped to it and is set to burst mode for three-round shots.
- CZ 75 Select Fire: A selective-fire variant of the renowned Czechoslovakian handgun, this weapon can be fired semi-automatically, or full-auto when you hold down the trigger. It is actually named the CZ 75 Automatic in real life.
- Smith & Wesson Model 500: The strongest production revolver in the world, built on Smith & Wesson's X-Frame, and chambered for the extremely powerful .500 S&W Magnum. Even though it has very high recoil, leading to a slow firing rate, this gun is useful for getting instant kills and headshots. Comes equipped with a laser sight. Tip: If you have some enemies coming up behind you, and are bunched up closely enough, use the gun to take them out with one good blast.
- Thompson submachine gun: The .45 ACP submachine gun designed by John T. Thompson, made famous (or infamous, depending on the point of view) by the bootlegging gangsters of the Prohibition era. It is recommended to fire the weapon in short bursts, as the recoil from holding down the trigger long enough would cause the gun to rise, and as a result, you wouldn't hit anything.
- Izhmash PP-19 Bizon: A Russian submachine gun developed at the request of the Ministry of Internal Affairs (MVD), and created for counter-terrorism and law enforcement. It was created by a crack team of designers at Izhmash, lead by Viktor Kalishnikov (son of the AK-47's famous designer, Mikhail Kalishnikov) and Alexei Dragunov, the youngest son of Evgeny Dragunov, who designed the SVD Sniper Rifle. It is known for its distinctive helical-loading magazine that mounts beneath the barrel. Handles recoil better than the Thompson, and useful for crowds of enemies.
- Double Barrel 12 Gauge: A generic two-barreled, break-action shotgun using 12 Gauge shotshells. Can fire two shells at at time. If you want to use it to its full potential, stock up on ammo for it, and use the weapon at close range.
- Franchi SPAS-12: A dual-mode (semi-automatic or pump-action) combat shotgun produced by the Italian Franchi company from 1979 to 2000. Though its firing rate is rather low (the weapon is in pump-action mode), it's still useful for taking out enemies at close range.
- Pancor Jackhammer: One of the three most potent weapons in the game, a gas-operated full-auto shotgun with a firing rate of 240 rounds per minute, distinguished by its futuristic appearance. Very useful for mowing down multiple enemies at close range.
- Gryojet: A pistol from the Gyrojet family of firearms, capable of firing handgun-caliber Microjet rockets. It is useful for taking out crowds of enemies with a single shot.
- Milkor MGL: The South African revolver-type 40mm grenade launcher. Useful against crowds of enemies, but can only be used in Super Survival Mode.