The design of Spike Rosered, also known as Axle the Red, is based on that of Noriaki Kakyoin from JoJo's Bizarre Adventure.

Duff McWhalen/Tidal Makkoeen originally had a different unique theme, as opposed to the remix of Bubble Crab's theme from Mega Man X2 in the final game.

There is a glitch in the PAL version, that is not present in the American/Japanese versions.

Finishing a mission between 00'50"00-00'59"99 and 01'50"00-01'59"99, removes 50 seconds from the timer, giving the player an impression that they finished the mission faster.

Some of the music tracks in this game are remixes of music pieces from previous installments.
Duff McWhalen's theme is a remix of Bubble Crab's theme from Mega Man X2, Shadow Devil is a remix of the Wily Boss theme from Mega Man, Rangda Bangda is a remix of the Fortress Boss theme from Mega Man X, and the intro theme is a remix of the Variable X/Get Weapon music from Mega Man X/Mega Man 3.

The first two Sigma stages are both remakes of stages from other Mega Man games.

Stage 1 is a remake of Quick Man's stage in Mega Man 2. The boss, Black Devil, could be seen as a remake/redesign of the Yellow Devil from the original Mega Man, as both are weak against electric weapons. Once his health is low enough, the Black Devil will also turn into the Wily Machine 6 from Mega Man 6.

Stage 2 is a remake of Stage 1 of Sigma's Fortress from the original Mega Man X, and the boss is Rangda Bangda from the same game.

During the fight Spoiler:between X and Zero, a giant W appears in the back ground, similar to the Dr. Wily symbol. This was most likely intended to be a subtle reminder that Zero is Dr. Wily's last creation.

In the post battle speech with Dark Dizzy, Alia talks about how Sigma turned him Maverick three years before the game. During the battle, his health icon will be the normal Sigma logo that Mavericks have in the previous games, unlike the other bosses who have a skull.

When talking to Squid Adler with X, X will apologize for destroying Octopardo. This is a mistranslation as he is talking about Squid Adler's brother/friend (depending on the version), Launch Octopus, who is known as Launcher Octopuld in Japan.

This was meant to be the last game in the Mega Man X series. As such, plot lines were being wrapped up (Spoiler: such as Zero dieing and Sigma being defeated for good) and prepared for the next series, Mega Man Zero. However, Capcom later decided to green-light Mega Man X6 against Keiji Inafune's wishes, meaning he had to change his plans for the series.

In the North American localization of the game, the 8 Mavericks' names were translated by Alyson Court, voice actress for Claire Redfield in the Resident Evil series. The translated names were based on members of the rock band Guns N' Roses:

Crescent Grizzly -> Grizzly Slash (Saul "Slash" Hudson)
Bolt Kraken -> Squid Adler (Steven Adler)
Shining Hotarunicus -> Izzy Glow (Izzy Stradlin)
Tidal Makkoeen -> Duff McWhalen (Duff McKagen)
Spiral Pegacion -> The Skiver (Michael "High as the Sky" Monroe)
Spike Rosered -> Axle the Red (Axl Rose)
Dark Necrobat -> Dark Dizzy (Dizzy Reed)
Burn Dinorex -> Mattrex (Matt Sorum)

In the Japanese version of the game, there were narrator voices for each of the Maverick's names that you would hear during their intro sequence after you selected their stage. These were removed in the US release. In order played, the names are: Tidal Makkoeen, Dark Necrobat, Spike Rosered, Burn Dinorex, Dynamo, Shining Hotarunicus, Spiral Pegasus, Crescent Grizzly, and Bolt Kraken.