- Dead Space reference
In 'The Hive' chapter, after you tickle the first door, turn to your left, and walk forward. Crouch to get under the bridge, and you will see a dead EDF Soldier with Isaac Clarke's signature engineer helmet.

- Tommy Tutone reference
In the bathroom in the 'Duke Nukem's Titty City' chapter, above one of the urinals is some grafitti that reads 'Jenny - 867-5309'. This is a reference to the Tommy Tutone song of the same name.

- Starship Troopers reference
After killing some enemies, you will hear Duke say 'I'm from Las Vegas, and I say kill 'em all!'. This is a reference to Starship Troopers when Johnny Rico says 'I'm from Buenos Aires, and I say kill 'em all!'.

- Activate Cheats
Successfully complete the game on the indicated difficulty to unlock the corresponding cheats and bonuses at the 'Extras' menu. Notice: Enabling the 'Infinite Ammo', 'Instagib', or 'Invincibility' cheat options will prevent Ego points and trophies from being earned.

Invincibility (no damage from bullets or explosions)	Normal difficulty or higher
Duke Sound Board	Easy difficulty or higher
Movies	Easy difficulty or higher
Development Timeline	Easy difficulty or higher
Grayscale Mode (black and white graphics)	Normal difficulty or higher
Instagib (enemies killed with one shot and always gib)	Normal difficulty or higher
Duke 3D Freeze Ray (freeze ray fires bouncing ice projectiles)	Normal difficulty or higher
Head Scale (adjust head size of enemies and NPCs)	Easy difficulty or higher
Concept Arts	Easy difficulty or higher
Game Speed (adjust game speed)	Normal difficulty or higher
Infinite Ammo	Normal difficulty or higher
Screenshots	Easy difficulty or higher
Mirror Mode (graphics are mirrored horizontally)	Normal difficulty or higher
Triptych Office Photos	Easy difficulty or higher

- Easy 'Turd Burglar' trophy
Poop can be found in toilets. There is some poop in the toilets in the room where the game begins ('Duke Lives' chapter). Grab poop from a toilet and throw it to get the 'Turd Burglar' trophy.

- Inception reference
In the 'Duke Nukem's Titty City' chapter, enter the room where you can microwave the popcorn. Look on the desk where you can use the security camera, and you will see a spinning top, like the one Leonardo DiCaprio uses in Inception.

- Mortal Kombat reference
In the Duke Nukem soundboard, there is an entry called 'Fatality'. When you select it, Duke says 'Duke wins, Fatality.'

- Easy 'I Need A Date' trophy
In 'The Shrunk Machine' chapter, near the beginning, after entering the first large room, straight ahead across the room are some double doors. There is a calendar on the wall behind the double doors. Look at all pages to get the 'I Need A Date' trophy. There is another calendar in Part 2 of 'The Forkstop' chapter on the wall in one of the rooms.

- Microwaved rat
In Chapter 2: 'Damn! It's Late...', there is a room with a microwave. Directly under the microwave is a cupboard that can be opened to find a rat. You can pick up the rat and put it in the microwave. Notice: This room is also shared with the Duke Nukem Fanboy.

- Easy 'Air-Duke' trophy
In the 'Duke Nukem's Titty City' chapter, go to the game room at the back of the club, and play a game of air hockey. Instead of focusing on scoring, try defending your goal as good as possible. The rest will happen by accident since the opponent is very weak.

- Easy 'Sunday, Black Sunday' trophy
In the 'Duke Lives' chapter, at the very beginning of your first fight, you will see a blimp in the background. Keep shooting it until you get the 'Sunday, Black Sunday' trophy.

- Overdrive mode
Reach Level 40 in Multiplayer mode to unlock Overdrive mode. In this mode, all points earned are doubled with the exception of challenges. You will also get 20 points each time an enemy is damaged.

- Trophies
Successfully complete one of the following tasks to get a trophy:

Bronze Trophies
Nuclear Devastation	Kill 250 aliens.
Piece of Cake	Finish the SP campaign on Easy Difficulty.
Pescaphobe	Kill all of the catfish in the underwater level.
Big Guns, Big Ships	Blow up 5 enemy Gunships or Dropships.
Natural Disaster 3x	Kill 3 aliens at once.
Nobody Likes a Whiner	Knock out the talent at the talk show.
Sticky Bomb Like You!	Put a Trip Mine on a live alien.
Judge, Jury, Executioner	Execute 20 aliens.
Extermination	Kill 50 aliens.
Fork the Pork	Kill 6 aliens with the forklift.
Juiced	Take steroids in SP.
Road Rage	Kill 15 aliens with the monster truck.
Drawrings	Doodle something on the whiteboard in SP.
On the Noggin'	Kill 30 aliens with headshots.
Annihilation	Kill 100 aliens.
Freeze Well!	Kill 15 frozen aliens.
Companion Barrel	Unlock the secret closet at the end of the Forkstop.
I Need a Date	Look at every page of a calender in SP.
Dead Useful	Kill 10 aliens with environmental explosives.
I Need a Towel	Get hit by 10 Pregnator bombs.
Tosser...in the Literal Sense	Kill 10 aliens with tossed objects.
Sunday, Black Sunday	Shoot down the blimp above the stadium.
Bucket Head	Find all 3 helmets in the SP campaign.
Trapper	Kill 10 aliens with Trip Mines.
Full Body Tourettes	Get knocked down 10 times.
One-Eyed Freak	Overcome the Cycloid.
Hippy-Stomper	Foot stomp 12 aliens.
Substance Abuser	Drink beer while on steroids or vice-versa in SP.
He's Got a Hologram!	Use a Holoduke in SP.
Flagon of Chuckles	Drink a beer in SP.
Turd Burglar	Find and steal a piece of poo.
Lots of Whacking	Be victorious in a game of Alien Abortion in the strip club.
Duke Angry, Duke SmasH!	Kill 15 aliens with melee attacks while on steroids.
Party Animal	Drink all of the beers in the strip club.
Baron von Nukem	Shoot down 20 alien fighters.
Special Thanks	Watch the credits all the way through.
Pit Champion	Overcome the Battlelord in Las Vegas.
Noms	Eat 10 pieces of food in SP.
Silver Trophies
Gunslinger	Carry the gold pistol through the whole SP campaign.
Octacide	Overcome the Octaking.
Call Waiting	Listen to all phone messages.
Air-Duke	Be victorious in air hockey with a score of 7-0 in the strip club.
I Am All That Is Man	Discover all ego cap rewards.
A Good Dam Fight	Overcome the Battlelord on the Hoover Dam.
Balls of Steel	Gain a 1,000,000 pinball score in SP.
Let's Rock	Finish the SP campaign on Normal Difficulty.
Clearing the One-Eyed Worm	Overcome the Leech.
Not Bad for a Human	Overcome the Alien Queen.
Gold Trophies
Come Get Some	Finish the SP campaign on Hard Difficulty.
Damn, I'm Good	Finish the SP campaign on Insane Difficulty.
Platinum Trophies
Savior of the Universe	You got them all.

- Bonus accessories
Successfully complete the indicated multiplayer weapon challenge to unlock the corresponding accessory in the changing room:

Ski Goggles	Execute a frozen player 75 times (Ice To See You III).
Cheese Hat	Get 250 kills with the Ripper (Swiss Cheese III).
Tie-Dye Shirt	Get 250 kills with the AT laser (Medium Rare III).
Uncle Sam Hat	Stomp on 75 enemies (Pee Wee Vermin III).
Brain Sucker	Get 250 kills with the Enforcer (Laser Seeking Missiles III).
Hoplite Helmet	Get 75 melee kills (Punchy McPuncher III).
Military Hat	Get 250 kills with the Pistol (Size Doesn't Matter III).
Canadian Flag Logo	Get 75 kills with the Garter Pistol (Tiny But Deadly III).
Backwards Baseball Cap	Get 250 kills with the Shotgun (Burger Face III).
I Shot Stupid Logo	Get 250 kills with the Railgun (Right In The Eye III).
Baseball Cap	Get 75 kills with pipe bombs (Splatter King III).
Detonator Logo	Get 250 kills with the Rocket Launcher (Boom Goes The Weasel III).
Jester Hat	Get 75 kills with trip mines (Watch Your Step III).
Wolf Logo	Get 75 kills with Steroids (Roid Rage III).
Retro Duke Logo	Get 250 kills with the Devestator (Meat Grinder III).
WTF Logo	Get 75 kills with exploding barrels (Smile You Son Of A Bitch III).

- Halo reference
At the begin of the 'Vegas In Ruins' chapter, before you enter the building, there is a van with weapons. The armor in the van is the same from Halo, other than the Nukem insignia on the helmet visor.

- Christian Bale reference
In Chapter 2: 'Damn! It's Late...', after walking off the set, you will see an actor yelling at someone. He says things like 'Do you want me to trash your mics? DO YOU?' and 'You're a nice guy, you really are but you're a f**king amateur'. This is a reference to when Christian Bale freaked out on the set of Terminator: Salvation.

- Easy 'Sticky Bomb Like You!' trophy
At the beginning of 'The Duke Dome' chapter, you will get an infinite amount of explosives when entering a building. Throw a trip mine directly on one of the enemies to get the 'Sticky Bomb Like You!' trophy.

- 300 reference
Duke will say 'Tonight, you dine in Hell' after a kill in the 'Vegas In Ruins' chapter. This is a reference to 300, when Leonidas says 'Tonight, we dine in Hell!'