The two sides were both in FA Cup action earlier in the week, with Boro securing a famous win over Spurs to progress to this evening's quarter-final draw, while the Hatters lost a 3-2 thriller to Champions League holders Chelsea.
Back in the league, Middlesbrough are just two points off the play-off places, while their opponents are sitting in sixth place. The result of the game, therefore, could go a long way in deciding whether either of the two sides secures a top six finish by the end of the season.
Speaking after the shock victory over Spurs, Boro boss Chris Wilder said: “A home draw would be nice, you're not fussy though.
“We’re in the quarter final of the FA Cup. We’ve gone deep into the competition. We’ve had a couple of fabulous nights and I quite enjoyed the third round against Mansfield where that was a different type of game to Old Trafford and tonight.
“To get to the quarter finals, you’ve got to go through different obstacles, hurdles and different challenges and that (Mansfield) was a huge challenge for us on that day coming off the back of the Covid situation locally and the team that we picked to go through.
“Then to go to Old Trafford and beat Tottenham. We are deep in the competition now."
Take a look at the latest news and transfer stories from the second tier, ahead of another busy midweek packed with fixtures:
5. Battle for Semenyo intensifies
RB Salzburg are the latest side to be credited with an interest in an interest in Bristol City striker Antoine Semenyo. He’s bagged six goals and made eight assists so far this season, which has seen him also attract interest from Celtic and West Ham. (FootballScotland) | Getty Images
6. Forest could bring Garner back if promoted
Nottingham Forest’s hopes of bringing star loanee James Garner back for another season could rest upon whether they can secure promotion. Man Utd are said to be hopeful of the player gaining top tier experience on loan next season. (The Athletic) | Getty Images
7. Forest star in no rush over future decision
Nottingham Forest sensation Brennan Johnson is said to be in “no rush” to sign a new deal. The Forest star has attracted interest from the likes of Leeds United, West Ham and Brentford, and looks likely to keep his future options open. (The 72) | Getty Images
8. Saints keen on Terriers loan man
Southampton are believed to be interested in signing Chelsea midfielder Tino Anjorin. He’s currently on loan at Huddersfield Town, but hasn’t featured since joining last month due to injury issues. (Evening Standard) | Getty Images