The project director for Fallout: New Vegas, J.E. Sawyer, released a mod for the game which brings more difficulty, shifts certain NPC alignments and modifies a few character stats.

The reason this wasn't released as an official patch was partly due to its technical difficulties and difficulty curve, however it was mainly due to the development for the game and all DLC having ended.

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.