Techland took inspiration from novels such as Albert Camus' "The Plague" and Joseph Conrad's "Heart of Darkness" for the game's story in order to "evoke similar emotions" and show how people can react to extreme situations.

Certain female zombies with skirts in the game have visible, modeled vulvas.

During the Rupert the Gunsmith sub-mission, a pink teddy bear can be found in Rupert's apartment. Activating this bear will make it say "I love you.". As the player continues to activate this bear, the bear's dialogue will change, and it will insist you stop touching it. If you proceed to activate it after this warning, its eyes will turn red, and the bear will explode.

Due to complaints and negative reviews on Amazon, an update was released for the Japanese version that reverted the game's green blood and gore back to red after it was previously censored.

Several boxes of medicine can be found throughout the game with the name "Techlax" on them. This is a reference to the game's developer, Techland, combined with the name ex-lax, a popular brand of laxatives.

A set of sticky notes found within the tower block headquarters read:
"1. Phase One
2. ????
3. Profit"

This is a reference to The Underpants Gnomes featured in Southpark who have a plan of stealing underpants, then an unknown step, resulting in profit.

During a mission where Spoiler:the player has to rescue Dr. Zere from Rais there is an area that looks like an office, which includes a desk with a bloody pencil. This is a reference to the Batman movie "The Dark Knight", where The Joker Spoiler: kills one of Gambol's bodyguards with a pencil.

During the "Bunker" side quest, on the uppermost accessible floor is an elevator crawling with bugs. Inside the elevator is an enemy resembling a Clicker from The Last of Us. When the enemy is killed and looted, a weapon modification called "Clicker" can be obtained.

In the Japanese release, all of the blood in the game was changed to green instead of red.

A bakery can be found called "Left4Bread", a reference to Valve's co-op zombie shooter series, Left 4 Dead.

A green warp pipe can be found inside a chimney. When the player enters the pipe they will be warped to a first person version of the first level of the original Super Mario Bros. Inside this level is a hidden block that must be jumped into from underneath to reveal. Once revealed, blueprints can be found on top of it for the "Pyza Suit", which references the Tanooki Suit from Super Mario Bros. 3. It allows the player to hover over large distances.