There's a fossilized dog called Seymour in the Lonesome Road DLC. Seymour has the appearance of a normal dog, but at a reduced size. His inclusion in the game is a reference to the Futurama episode "Jurassic Bark" in which Fry finds his dog Seymour fossilized and tries to clone him.

The weapon Fat Man and its mod Little Boy are named after two atomic bombs that were dropped on Hiroshima (August 6th) and Nagasaki (August 9th) in Japan during the end of the World War II. In the Japanese version, the name Fat Man is changed to "Nuka Launcher," yet the Little Boy Kit kept its name. The changes were made to avoid offending the people of Japan, though Japanese gamers generally didn't approve of the change.

During the opening, you are shown inkblots in order to test your mental health. Fans thought that one of the inkblots looked like two bears high-fiving, but this was not an option in the game. A fan decided to make a mod for the game which made 'Two Bears High-Fiving' an option. Obsidian referenced the fan reaction and the mod by putting a character called 'Two-Bears-High-Fiving' in the game's Honest Hearts DLC.

During an interview with Variety Fair, Todd Howard revealed that the 2024 live-action "Fallout" TV series was considered canon to the games, having wanted to tell an original story within the game's world rather than adapt any of the previous games. However, when the show came out, this lead to complaints from fans accusing the show of retconning the events of Fallout: New Vegas. Specifically, the sixth episode "The Trap" featured a shot of a blackboard seemingly depicting the fall of Shady Sands (the capital of the New California Republic) as taking place in the year 2277. Fallout: New Vegas takes place in the year 2281, yet Shady Sands is stated to still exist in the game without any mention of a fall (although the city cannot be visited in-game). Emil Pagliarulo, a design director for Bethesda, would try to assure fans on Twitter that Fallout: New Vegas is still considered canon, claiming to being overprotective of the series' lore and going as far as to post a timeline of the Fallout series. While the timeline not only featured both Fallout: New Vegas, the TV series, and also confirmed that Fallout Tactics: Brotherhood of Steel is considered canon to the series, it did not address the timeline inconsistency brought about by the blackboard scene in the show. This reportedly lead some fans to accuse Bethesda of holding a grudge against Obsidian Entertainment for making what many fans consider to be the best Fallout game and using the show as a way to spite them. However, it's worth noting that there are three other possible explanations for the inconsistency:

• Whoever wrote "2277" was misinformed due to the post-apocalyptic setting forcing many to rely on guesswork for event dates.
• It could be a simple mistake in writing for a series with large amounts of lore to it.
• It could be a reference to the "Lonesome Road" DLC expansion for New Vegas, where the player is given the option to nuke the NCR, though there is no confirmation that this ending is canon.

Howard would later defend the TV series and insist the game is still canon in an interview with IGN, claiming he had an emotional reaction when the TV series writers brought up the idea of bombing Shady Sands (which he also clarified was not a nuclear bombing) and carefully talked through the decision with them. When asked specifically about the 2277/2281 inconsistency, his response was that they were "threading [the needle] tighter there" to make it land in the TV series, move the Fallout series forward, and insisted that the fall of Shady Sands took place just after the events of the game. He reiterated that Bethesda was careful about sticking to the series timeline, admitting that there "might be a little bit of confusion at some places" and claimed that what was most important to them was what was happening in the time period of the TV series.