The third and fourth-placed sides head into the fixture at Kenilworth Road trailing the Blades by seven and eight points respectively in the Championship standings.
Match preview
Automatic promotion was always going to be a long shot for Luton, but the 1-1 draw at Reading last time out effectively ensured that a playoff place would be the most realistic outcome.
Rob Edwards's side found themselves trailing to an Andy Carroll goal, only for the forward to soon get himself sent off and aid Luton's efforts to equalise, which came from the penalty spot 10 minutes from time.
Successive wins for Sheffield United means that the minor setback will likely prove irrelevant, with the Blades seven points clear of Luton with a match in hand.
Nevertheless, Luton can be delighted that they remain on an 11-game unbeaten streak, a run which has featured seven victories and four draws.
A home second leg in the playoffs is also pretty much guaranteed, and the upcoming triple-header to end the regular season is about maintaining their high performance levels.
Barring the point difference between the two clubs, Middlesbrough are in an identical situation, the hard work having already been done to earn a playoff spot.
Michael Carrick's team have more to work towards in the sense that they recently endured a three-match winless streak before bouncing back with home victories over Norwich City and Hull City.
A total of eight goals were scored in those triumphs, five strikes coming in a 42-minute period versus the Canaries and three efforts being recorded in six second-half minutes against the Tigers.
Ahead of the weekend fixtures, Boro still require one more win to guarantee a top-four position, yet Carrick will be more focused on the display of his side against potential future opponents in the playoff final.
Luton Town Championship form:
D
W
D
W
W
D
Middlesbrough Championship form:
W
L
L
D
W
W
Team News
Given the level of opponent, Edwards is unlikely to make any major changes to his Luton XI for this contest.
Elijah Adebayo may be considered for a recall after making an impact off the substitutes' bench at Reading, while Luke Freeman and Luke Berry are options in midfield.
Carrick is expected to tinker with his Middlesbrough side with his half-time alterations making the difference in the win over Hull.
Isaiah Jones could earn a start down the right after providing two assists upon his introduction, with Marcus Forss potentially switching to the left.
That would allow Hayden Hackney to revert back to central midfield, taking the place of Alex Mowatt in the process.
Luton Town possible starting lineup:
Horvath; Lockyer, Bradley, Bell; Drameh, Nakamba, Mpanzu, Doughty; Campbell; Morris, Woodrow
Middlesbrough possible starting lineup:
Steffen; Smith, McNair, Lenihan, Giles; Howson, Hackney; Jones, Akpom, Forss; Archer
We say: Luton Town 1-1 Middlesbrough
While this is a key fixture for both sides, there may be acknowledgement that solidifying their current spots is more important than making an unlikely bid to topple the Blades. With that in mind, do not be surprised to see a low-scoring draw play out between two strong teams.