Before the final phase of the Omega boss fight, Omega Zero exclaims, "Ware wa meshia nari!" which means "I am the Messiah!" This quote is also used before the battle against Omega Zero in Mega Man ZX. This fortifies the fact that many characters refer to Omega as "The God of Destruction". The reason behind him saying that inside Zero's original body may be due to the fact that Dr. Wily originally made Zero as a "God of Destruction" and when Omega (being a consciousness) was put into Zero's original body he sought out to fulfill Zero's original purpose.

According to the original packaging of the game, it was referred to as the "exciting conclusion to the Zero series". Due to fans demanding another game in the series, Inti Creates created Mega Man Zero 4 with the intention of truly ending the Zero series.

Due to the fact that Omega uses Zero's original body, this is the only game in the series where two of the same characters from different eras meet in the same game (X-era's X and Zero meet Zero-era's X and Zero).

Technically, with the destruction of Zero's original body, Dr. Wily's creations outlasted Dr. Light's creations with X's body being destroyed in Mega Man Zero 2.

Deathtanz Mantisk's name was misnamed as "Deastants Mantisk" in the English instruction manual.

Deathtanz Mantisk often says the Japanese onomatopoeic phrase "chikachika". This is often used in Japanese graphic novels and comics to indicate the twitching of someone's eyes. Apparently Mantisk has made a habit of saying this every time something annoys him enough to make his eye twitch.

Dr. Weil, like many characters, underwent several different designs in the conceptual stages. His designs were based on three different ages: young, middle-aged, and old. Ultimately a variation of the old design was chosen, but there are notes of interest about his other designs as well. The young design was meant to pilot a giant exoskeleton, and before being revealed as a young man his silhouette was meant to be seen with glowing eyes that made him appear more monstrous. The middle-aged design bears some mild similarities to Doctor Wily, though Inafune has firmly denied Weil and Wily were directly connected in any way. This design was later used for a minor character in Mega Man ZX Advent.

Though their fate is never made clear in either Mega Man Zero 3, in an interview it was revealed that the three remaining X Guardians died shielding Zero from Omega exploding, explaining their absence from Mega Man Zero 4.