The Boro knocked Tottenham Hotspur out of the FA Cup following a 1-0 extra-time win as 19-year-old Josh Coburn came off the bench to make a difference.
It came just days after their 3-2 loss to Barnsley in the league and will be hoping to return to winning ways in the league too.
Luton are two points and two positions ahead of Chris Wilder's side in the league table, coming into Saturday on the back of three consecutive wins.
Middlesbrough vs Luton Town Head-To-Head
There have been 32 clashes between the sides before, with Luton winning 14 times and losing on 10 occasions.
In their November reverse, however, the Hatters secured a 3-1 win at home and are aiming for their first league double over Boro since the 1962-63 season.
Middlesbrough Form Guide (all competitions): W-L-W-L-W
Luton Town Form Guide (all competitions): L-W-W-W-L
Middlesbrough vs Luton Town Team News
Martin Payero is out due to injury while Riley McGree is a doubt after missing Boro's last two games.
Head coach Chris Wilder could opt to play the same XI that beat Tottenham Hotspur in the FA Cup on Wednesday.
Josh Coburn has made a case for the starting XI following his heroics as he scored the winner of their 1-0 win in the 107th minute.
Injured: Martin Payero
Doubtful: Riley McGree
The Hatters' performance against Chelsea wasn't bad by any stretch of imagination. Hence, Nathan Jones wouldn't feel like making any changes.
Robert Snodgrass will be gunning to start over Peter Kioso on the right wing. Harry Isted could continue between the sticks as Jed Steer went off injured in the last match.
Sonny Bradley is also out due to a hernia problem, while Henri Lansbury and Pelly Ruddock-Mpanzu remain doubts for the game.
Injured: Jed Steer, Sonny Bradley
Doubtful: Henri Lansbury, Pelly Ruddock-Mpanzu
Middlesbrough vs Luton Town Predicted XI
Middlesbrough (3-5-2): Joe Lumley; Anfernee Dijksteel, Paddy McNair, Dael Fry; Isaiah Jones, Matt Crooks, Marcus Tavernier, Jonathan Howson, Neil Taylor; Duncan Watmore, Josh Coburn.
Luton Town (3-5-2): Harry Isted; Dan Potts, Reece Burke, Tom Lockyer; Robert Snodgrass, Luke Berry, Carlos Mendes, Gabriel Osho, Amari'i Bell; Harry Cornick, Admiral Muskwe.
Middlesbrough vs Luton Town Prediction
Both teams put up a valiant performance against their respective Premier League opposition in midweek and will inspire them to turn in their best once more on Saturday.
Armed with a menacing attacking arsenal, the sides might as well play out a high-scoring draw.
Prediction: Middlesbrough 2-2 Luton Town