According to former character artist Jonah Lobe, the response from Fallout fans and the fan website "No Mutants Allowed" to Bethesda purchasing the series from Interplay Entertainment and developing Fallout 3 consisted of "a lot of excitement, a lot of enthusiasm, and a lot of death threats." Lobe claimed that while he and other employees at Bethesda were not "privy" to most of the details on the threats due to the company shielding them from its workforce, as a result of the overwhelmingly vocal and mixed responses from fans, Bethesda had to hire a security guard for the first time in its 21-year history.

An unused set of Enclave Power Armor can be found in the game files and spawned in-game, utilizing console commands.

The stats differ and the armor set carries the file name, "Robo-Thor Armor", evidently a reference to Marvel Comic's Thor, as the armor helmet has a unique design reflective of Thor's own signature helmet.

In the Broken Steel DLC, in the cutscene used for when the player character travels on the Presidential metro, the moving train is not a separate entity programmed to move on its own due to limitations with the Gamebryo engine. Instead, when the player goes on the metro, a script is triggered that equips an NPC underneath the train with a glove that turns its right hand invisible and produces the model for the Presidential metro car on top of it appearing like a giant hat. This then triggers an animation of the NPC's model sitting down and gliding along the ground in an arc that simulates the metro riding along the subway tracks.

Rivet City's Abraham Washington is the name of this NPC and is a reference to two former United States Presidents, George Washington and Abraham Lincoln.

Concept art was produced showing that there was a possible third size-class for the Super Mutants, labelled as a "Spinebreaker." In terms of size, the Super Mutant Spinebreaker would have been somewhere between the regular Super Mutant Grunts and Super Mutant Behemoths, effectively being the second size class of Super Mutants.

Concept art and unused models exist for cut weapons referred to as the "Kryolator" and "Kryo-Grenade." While the grenade itself made it into the Mothership Zeta DLC with a new texture and mesh, the "Kryolator" was ultimately cut in the final version of the game, existing as only a mesh with textures. However it did later appear as a usable weapon in Fallout 4.

The Wanamingo from Fallout 2 was at one point planned to be in the game, but was never added into the final version. Concept art shows it as a possible variant of the original, being much bigger and without tentacles.

The names of many unique weapons are clear references:
•"Occam's Razor" is a reference to the scientific principle of the same name.
•The "Board of Education" is a reference to the paddles once used for corporal punishment, as well as the government body that oversees schools in a specific area.
•A Ripper called "Jack" is a reference to Jack the Ripper.
•A metal saw called the "Man Opener" is a play on "can opener".
•A pool cue called "The Break" is a reference to the Pool term of the same name.

In "The Pitt" DLC the player can collect 100 steel ingots and return them to a man named Everett. After turning in all 100 Everett says "Yup, guess you got every last one out there. You're one hell of a steeler, kid." The name 'steeler' is a common nickname for steel workers, but is also a reference to the NFL team, the Pittsburgh Steelers.

Dogmeat is an Australian cattle dog, and was modelled after the dog from Mad Max 2. He is also named after the dog from "A Boy and His Dog", a 1975 post-apocalyptic movie.

According to Emil Pagliarulo, the lead designer for Fallout 3, Tranquility Lane's Betty was inspired by the character Billy Mumy from the Twilight Zone episode "It's a Good Life." In the episode, Billy, a "little kid with godlike powers terrorizes the inhabitants of a town, and 'wishes' them into the cornfield when they're bad."

Originally Liberty Prime was planned to be massive and would allow players to ride inside his head during the final mission, but this idea was scrapped before the game's release.

The scenario at the beginning of the game where Butch steals the player's sweetroll is a reference to a running gag in The Elder Scrolls series, where the game asks what the player would do when someone tries to take their sweetroll.

The mutant fire-ant centered quest called "Those!" is a reference to the 1954 film titled "Them!", in which ants are mutated by atomic tests in New Mexico, which in turn makes them gigantic and wreck havoc upon civilization.

The arts-centered Vault 92 holds a number of musical and sound-related references;
• The Overseer of Vault 92 is named "Richard Rubin", who is likely named after music producer Rick Rubin.
• "Zoe Hammerstein" gets her name from Broadway lyricist and songwriter Oscar Hammerstein II, who helped make the song "I'm in Love with a Wonderful Guy", which is played in-game on the GNR Radio Station.
• "Gordon Sumner" is actually the real name of the musician known as Sting.
• "Professor John Malleus" is named after the one of the three auditory ossicles, (small bones located in the middle ear) which transmit sounds from the air to the inner ear. The Malleus is the "hammer" in the set of "hammer, anvil, and stirrup," so named after their shapes.

Several references to horror stories and movies can be found in the game. In the Point Lookout DLC, a unique knife called the "Toy Knife" can be found alongside a Hockey Mask, referencing Jason Voorhees from the movie series Friday the 13th.

Another reference is found in both the standalone Fallout 3 and in Point Lookout, the first being in a simulation called Tranquility Lane, in which the player can don a clown mask as a kid and begin a killing-spree within the simulation. The second time the mask pops up is in Point Lookout, which is found on top of a skeleton in a bathtub inside a motel room, which itself is adorned with skeletons and blood splattering. This is a reference to Michael Myers from the Halloween movie series, and more specifically his first kill where he wore a clown suit and mask, doing so as a kid.

H.P. Lovecraft references appears in the standalone Fallout 3 too, with the inclusion of the Dunwich Building. The story told through the building via Audio Logs and the apparent obelisk near the end references the Cthulhu Mythos, more specifically the story called The Dunwich Horror, which the very building is named after. The player can also hear the word "Alhazred" from the Obelisk alongside one of the last audio logs, which refers to the fictional author of the Necronomicon, who is named Alhazred. The narrative is extended even further with the inclusion of the Point Lookout DLC, which includes an actual quest line involving a tome named The Krivbeknih and the owner of the book, Obadiah Blackhall. The Krivbeknih is in reference to the number of various books/tomes and artifacts featured predominately in Lovecraftian stories, and the Blackhall family is another reference to The Dunwich Horror, namely that of the Wheatley Family, as well as a possible reference to the central family in The Lurker at the Threshold, which involves an aristocratic man that inherits his family's dark legacies.

A modified Mister Gutsy, named "Sawbones", can be found at the Citadel. When first encountered, it greets the player with the phrase "Please state the nature of the medical emergency." This is a reference to the EMH Mk 1 program (aka The Doctor) from Star Trek: Voyager. In addition to the phrase, it also shares a similar personality to The Doctor which includes the bad bedside manners, as well as an interest in arts (in Sawbone's case, writing poetry) which separates it from normal Mister Gutsys, much like how The Doctor stood out among his EMH counterparts.

The inhabitants of the Temple of the Union are named after Abraham Lincoln's cabinet;
Hannibal Hamlin was Vice President, Caleb Smith was Secretary of the Interior, William "Bill" Seward was Secretary of State, and Simon(e) Cameron was Secretary of War. On top of this, the dog found there is named "Four Score", which is a reference to Abraham Lincoln's opening of the Gettysburg Address ("Four score and seven years ago...").

In Megaton, the undetonated atomic bomb and the Children of Atom are a reference to the film "Beneath the Planet of the Apes", in which a cult worships an intact nuclear ICBM.

The village of Arefu is an actual real-world place inside of Romania, most well known for its proximity to the former castle of Vlad III, who is also known as "Dracula" and "Vlad the Impaler." It is also the main stage for the questline "Blood Ties", which deals with a group of cannibals who believe themselves to be vampires. One of the NPCs involved with the questline, Lucy West, is likely based off of Lucy Westenra, a character from Bram Stoker's Dracula.

The group of vampires call themselves, "The Family", are likely a reference to the 1971 Charlton Heston film The Omega Man, featuring a nocturnal breed of pale, vampyric mutants that live underground, referring to themselves as "The Family." Lastly, the password to open a locked-door containing one of the quest-line NPCs is "Vespertilio," which is a genus of the bat family.

A cafeteria bulletin board found in Vault 101 shows an advertisement for a Bingo Night, with the first prize being "a week's supply of Water Rations."
The "13" bingo-ball on the advertisement strongly suggests a call-back to the original Fallout, which starts out with Vault 13's Water Chip failing and requiring the Vault Dweller to go out and search for a new one.