The two confirmed Final Four participants are likely to be joined by experienced programs in Minneapolis on Saturday.
Texas Tech booked its first-ever trip to the Final Four with a win over Gonzaga on Saturday, while Virginia secured its first visit to the final weekend of the NCAA men's basketball tournament since 1984.
One of the two other Final Four berths will be handed to Duke or Michigan State, who have been pillars of consistency in the competition for decades.
Kentucky has also been a fixture at the Final Four in recent years, but in order to earn a spot in the Final Four, it has to beat an Auburn team that is looking to qualify for its first Final Four.
2019 NCAA Men's Basketball Tournament Bracket
Last 2 Teams Headed to Final Four
A fifth Final Four appearance this decade is in the sights of the Kentucky Wildcats, and it appears that they have the upper hand going into Sunday's Midwest Region final against Auburn.
With PJ Washington back from injury, the Wildcats held off a challenge from Houston to set up a third meeting with Auburn.
Washington is important to Kentucky's success because he provides support on the glass alongside Reid Travis and is the team's top scorer.
In 26 minutes off the bench Friday, Washington produced 16 points while shooting 6-for-8 from the field.
If Washington is once again able to complement the shooting of Tyler Herro, who led Kentucky with 19 points in the Sweet 16, the Wildcats will be able to challenge the Tigers in all facets of the offensive game.
If you add in double-digit point production from either Ashton Hagans or Keldon Johnson, both of whom scored more than 10 points in a game against Auburn, the Wildcats have a combination that should send them into the Final Four.
Defensively, the Wildcats have a blue print for stopping Auburn's fast-paced offense, as they held Bruce Pearl's team to 53 points the second time the two teams met.
Auburn also enters with a significant disadvantage, as Chuma Okeke suffered a torn ACL in the Sweet 16 win over North Carolina, per The Athletic's Shams Charania.
Trying to replace the impact of a player who contributed 20 points and 11 rebounds Friday in less than 48 hours is going to be tough for Pearl and his staff.
Auburn can still try to run Kentucky's defense up and down the court and score plenty of transition buckets, but without a powerful presence in Okeke down low, the Tigers won't be able to create many second-chance opportunities against Travis and Washington.
A win would set up Kentucky with a Final Four clash against Tony Bennett's Virginia Cavaliers.
Duke is likely going to have to battle through a third consecutive close game to reach Minneapolis.
The Blue Devils' reward for surviving threats from UCF and Virginia Tech is a showdown with an experienced Michigan State team.
In Zion Williamson and R.J. Barrett, the Blue Devils have the two best players on the floor, but they are going to need to overcome the defensive adjustments Tom Izzo and his coaching staff make after watching film of Duke's past two games.
Williamson and Barrett have led Mike Krzyzewski's team in scoring in each of its three NCAA tournament games, but the added scoring boost from Tre Jones will be key as well.
Jones exploded for 22 points with five three-pointers in the Sweet 16 victory over Virginia Tech, and he will carry plenty of personal motivation to get to the Final Four since he's from Minnesota.
The offensive contribution from Jones means more to Duke since Cam Reddish is a game-time decision with a knee injury, per The Athletic's Brendan Quinn.
If Reddish returns to action, there's no guarantee he will be at 100 percent since he sat out the Sweet 16 game, which means the Blue Devils need Jones to step up as a third scorer once again.
The key for Duke on the defensive side of the floor will be its perimeter defense, as it faces a Michigan State team that made 13 three-point shots versus LSU Friday.
If Duke forces Michigan State to take contested shots from three-point range and limits its second-chance opportunities by smothering the boards through Williamson and Barrett, the Blue Devils should control the contest.