This will be Holm's first fight in 19 months after a kidney issue ruled her out of competition.
The former bantamweight champion returns to a division that has seen a lot of change since her last fight, with a host of new prospects and contenders in the rankings and a new champion in Juliana Pena.
Holm (14-5) could make it three successive wins at the UFC Apex Center on Saturday night if she gets the victory over Vieira, and should Pena vs Amanda Nunes 2 go the way of the current champion, she could be in prime position for a title shot.
Ahead of the fight, Holm revealed to the media: "I have to win regardless because I hate to lose anyway.
"I just hate to lose period, no matter what is on the line.
"Whether I'm in practice training, I want to win the rounds and I want to win if I'm in front of two people or two million people.
"I want to get in there and I want to win on Saturday."
"The Preacher's Daughter" has taken on a who's who in WMMA, beating the likes of Ronda Rousey, whilst also squaring off with Amanda Nunes, Miesha Tate, Cris Cyborg and Valentina Shevchenko.
Stylistically wise, Saturday could be a great fight stylistically with the women being close on the stats in significant strikes landed per minute.
Holm averages 3.16 while Vieira averages 3.07, and both fighters having a striking accuracy of 38%.
Vieira will be looking to get back to back wins following her win over Tate in November last year.
Further down the card, Santiago Ponzinibbio and Michel Perreira will collide in what is sure to be a fantastic welterweight showdown. Elsewhere, young prospects Chase Hooper and Elise Reed will also be in action.
Saturday's card gets started at 21:00 BST on UFC Fight Pass, with the prelims starting on BT Sport 1 at 22:00 BST with the main card kicking off at midnight.
Holly Holm vs Ketlen Vieira - women's bantamweight bout
Santiago Ponzinibbio vs Michel Pereira - welterweight bout
Chidi Njukani vs Dusko Todorovic - middleweight bout
Polyana Viana vs Tabatha Ricci - strawweight bout
Eryk Anders vs Jun Yong Park - middleweight bout
Joseph Holmes vs Alen Amedovski - middleweight bout
Parker Porter vs Jailton Almeida - heavyweight bout
Omar Morales vs Uros Medic - lightweight bout
Jonathan Martinez vs Vince Morales - bantamweight bout
Chase Hooper vs Felipe Colares - featherweight bout
Elise Reed vs Sam Hughes - strawweight bout