As you play through the game, keep an eye out for references to other video games from various eras, including:
- Assassin's Creed - There is conversation about collecting flags and feathers, which were collectible items in the first two Assassin's Creed games.
- Mass Effect 2 - Rex complains that "they spent 10 million credits to bring me back to life and this is what I am doing?"
- Saint's Row: The Third - One enemy unit is known as The Running Dead, which is the same name as the zombies in Saint's Row: The Third.
- Mortal Kombat - There are numerous references, including the mission objective (Round 1: Fight), and the words the Mystic Door shouts near the end of the game (Test your might!).
- The Elder Scrolls: Skyrim - At coordinates X:522.4, Y:417.2, check the nearby area to find a soldier bent over with an arrow protruding from his knee.
- Hobo with a Shotgun Reference - The 80s movie, Hobo with a Shotgun, was an inspiration for this game's creative director, and is referenced by the Summon the Plague! mission title.
- Terminator 2 References - You will find the Galleria 1991 shotgun on your adventure, and that is a reference to the movie Terminator 2: Judgment Day. In the film, there is a shootout in the Galleria mall, and the movie was originally released in 1991. Also, the Cyber-Eye ability takes on an appearance similar to the scan performed by the Terminator in the movie.
- RoboCop Reference - The pistol that Rex carries bears a striking resemblence to the weapon used by RoboCop in the old action movies. Its burst-fire function in particular shows that connection. There are other nods to the film, as well. The weapon's description notes that it "was built and named in honor of a fallen DPD cop who fell in the line of duty fighting the creeps of the Detroit megaslums and industrial wastelands." The weapon is called the A.J.M. 9, in reference to RoboCop's name: Alex J. Murphy.
- Predator References - If you ever saw the movie Predator, which starred Arnold Schwarzenegger and Carl Weathers (among others), you witnessed one of cinema's most famous handshakes. You can witness it again here, in 16-bit form, during the first five minutes or so of play. There's another reference to the film, as well. During the chopper assault sequence, pay attention to the song that plays. It is Long Tall Sally, performed by Little Richard. You might recognize it from the moment in the movie when the commando team heads into the jungle.
- Teenage Mutant Ninja Turtles - Head to the coordinates X:519.9, Y:365.6, where you will find a garrison and the Predator's Path quest. Your goal is to kill turtles that have been befriending rats in the nearby sewers. When you find the turtles, you will see that their faces are painted hues similar to the headbands worn by the famous turtles from the comics and cartoons.
There are 18 Bronze Trophies and 1 Silver Trophy.
- Silver - Blood Dragon Down - Kill Your First Dragon
- Bronze - Derp - Jump Down from 50 Meters
- Bronze - Dragon Slayer - Kill 25 Dragons
- Bronze - Hail to the King - Reach Maximum Level and Become the Ultimate Badass
- Bronze - Just the Tip - Kill a Dragon with the Bow
- Bronze - Kill Them All - Finish all the Predator's Path Quests
- Bronze - Murder Nature - Kill all the Animal Types
- Bronze - Nice Like Jesus - Finish all the Hostages Situations
- Bronze - Running man - After saving Darling, enter Combat Mode with a Dragon and Return to Stealth
- Bronze - Set Them Free - Destroy 5 Braincages
- Bronze - The Drug of the Nation - Find all TV SETS to Decrypt the Hidden Message
- Bronze - The Greatest Format of all Time - Find all VHS Tapes
- Bronze - The Only True Stopper - Headshot Every Type of Enemy
- Bronze - Tooled Up - Own all Weapons Attachments
- Bronze - Way to Go, Garri-Son - Finish all the Garrisons
- Bronze - What are You Reading For? - Find all of Dr. Carlyle's Notes