Nuclear Throne takes you through a series of areas.
The way you progress through the areas is linear. You start in a normal world, which is three levels long; at the last level, the area boss will spawn. After defeating the boss, you enter a transition area, which is only one level but the level itself is larger. After that, you enter another world, and the cycle repeats itself.
Difficulty is the number of portals you have entered; it determines the amount of enemies spawning in the area and what kind of weapon you get in that area. Entering a Crown Vault or the Sewers Secret Area also counts as entering a portal and increases the difficulty by one, so you get better weapons faster, but there are more enemies.
To get here, you have to open the Ammo and Weapon Chests and the Radiation Canister on any Desert level without killing too many enemies, which is 2% of enemies on 1-1 and 1-2, and 10% on 1-3. Opening the chests will spawn Big Bandit. If you kill Big Bandit faster than 10 seconds, the portal to Oasis will open on his corpse.
If you didn't manage to kill Big Bandit in time, the regular level ending portal will teleport you to the Sewers, even if you spawned Big Bandit in 1-1 or 1-2.
The difficulty of this area is the same as in 1-2, 1-3, or 2-1.
The Weapon Chest in this area drops weapons from 2-1 and below.
Beating this area teleports you straight to 3-3, which means you skip any remaining Desert levels, the Sewers, and Scrapyard 3-1 and 3-2.
The game's difficulty does not compensate for this level skip, so while a secretless run will be at 7 difficulty by 3-3, a run which uses the Oasis path will only be at 5 difficulty.
You can get in by blowing up a round manhole cover that looks like a turtle's shell (sometimes it's hidden under a chest). This opens a portal and at the same time kills almost every enemy in the Sewers, which can be used to your advantage, as you don't have to enter the portal immediately.
Spawns between 2-1 and 3-1, but it has the same difficulty as 3-1.
The Weapon Chest in this area drops weapons from 3-1 and below.
After exiting Pizza Sewers, the game's difficulty is increased by one.
While looping the game, you can blow up the manhole only after killing the Mom boss.
This area and its enemies are designed in reference to Vlambeer's game called Gun Godz.
YV's Mansion contains a Golden Chest which will always give you a golden weapon.
You can get here by hitting the car wreck with golden trim in 3-1 with a Screwdriver, Golden Screwdriver, or Energy Screwdriver and pressing "E" when near the car. This opens a portal and at the same time kills almost every enemy in the Scrapyard.
The difficulty of this area is the same as in 3-2.
Beating this area teleports you straight to 3-3, which means you skip 3-2 and the game's difficulty increases at its normal rate.
This area is a version of Crystal Caves with inverted colors and cursed variations of Crystal Spiders and Laser Crystals.
You can get to this area if you have a Cursed Weapon while entering the level ending portal after the Big Dog boss fight (after 3-3). The portal transports you to this area instead of the regular Crystal Caves (4-1).
The difficulty of this area is the same as in regular 4-1.
Cursed Crystal Caves always have a Large Cursed Weapon Chest, which appears only in this level. It contains 3 Cursed Weapons that can be from 3 difficulties higher. If Cursed Crystal Caves are treated as 4-1 in terms of difficulty, this chest can drop weapons that are found in regular Weapon Chests in 5-3.
After clearing this area, you continue to 5-1 in the Frozen City, and the game's difficulty increases at its normal rate.
To get here, you have to feed the Frozen Corpse Flower with 4 HP by pressing "E" four times when near it. Each time you press the key, your character will take 1 damage. This opens a portal to the Jungle and at the same time kills almost every enemy in the Frozen City.
Entering the Jungle will remove Last Wish from your character's mutations. You will instantly choose a mutation that replaces it. Last Wish will be put back into the pool of mutations you can choose from, so it's possible to pick it again.
The difficulty of this area is the same as in regular 5-2.
After clearing this area, you continue to 5-3 in the Frozen City, which means you skip 5-2 and the game's difficulty increases at its normal rate.
Y.V's round cousin (called Yung Cuz) is also here, sitting on a couch, eating triangular chips and playing video games on a console plugged to a Giant Golden TV.
You can leave the level by pressing "E" near any of the Golden Cars parked in the garage and proceed to Y.V's Mansion. Blowing up the cars will respawn them after a few seconds.
This secret area is accessible only after looping the game.
To enter the HQ, you must press "E" at the back of an I.D.P.D. Van, in the short time when it is coming to a stop (the lights have to be on). A blue portal will open which takes you to the secret area.
HQ can be exited within the first 2 levels via the same method of entering. If HQ is entered on a X-3 level (ones that host bosses from preloop), the player will be sent back to this level; otherwise, they will be brought to the next area when exiting HQ. This adds an additional 1 to 3 difficulty to the run.
Trying to re-enter HQ will cause vans to explode on the player, making the area only possible to visit once per run.
The last level is the Captain's office. Defeating the Captain will end your run.