The Royals have won just one of their last seven games to lose ground on the playoffs, while Luton have climbed up to 13th thanks to back-to-back victories.
Veljko Paunovic's side have spent the majority of 2020-21 in the top six, and even enjoyed a spell in top spot, but it is looking like they will just miss out on the playoffs.
Friday's 1-1 home draw with Cardiff City leaves Reading four points behind sixth-placed Barnsley with four games to play.
Two of those games are against sides in the top three, so this really is a game the Royals have to win - plus hope for a helping hand from Huddersfield Town against Barnsley - if they are to stay in contention.
With Barnsley suffering a shock loss to Coventry City two days later, that point could yet prove to be huge for the Berkshire outfit.
One win in seven does not suggest that Reading have the ability to see out the season with a winning run, however, and Luton will certainly be no walkovers.
The Hatters followed up a 3-1 win at bottom side Wycombe Wanderers with a 1-0 victory at home to Watford on Saturday thanks to a late James Collins penalty.
Not only did that win earn Luton bragging rights against their neighbours, it also moved them just three points off ninth with a game in hand to play.
However, not since February 2019 have Nathan Jones's side won three league games in a row in a single season, which they are of course looking to achieve on Wednesday evening.
Luton also have a poor recent record against Reading, losing all three encounters since the start of last season by a 10-1 aggregate scoreline.
Collins is pushing for a recall to the side after scoring the winner against Watford, which could mean Kazenga LuaLua making way.
Glen Rea is another who is pushing for inclusion in central midfield, with Jones expected to stick with a 4-3-1-2 formation.
As for the visitors, Lucas Joao dislocated his shoulder last week in a further blow to their promotion hopes.
That will likely see George Puscas come in from the start at Kenilworth Road.
Meite should get the nod out on the right as he looks to add to the four goals he scored away at Luton in last season's fixture.
Luton Town possible starting lineup:
Sluga; Bree, Pearson, Bradley, Naismith; Clark, Dewsbury-Hall, Rea; Mpanzu; Adebayo, Collins
Reading possible starting lineup:
Cabral; Yiadom, Moore, Holmes, Richards; Rinomhota, Laurent; Meite, Olise, Ejaria; Puscas
We say: Luton Town 3-1 Reading
Reading have a good record against Luton and won 5-0 on their most recent visit to Kenilworth Road.
There is no chance of a repeat scoreline here, though, with the Hatters now in a far better shape.
Only three teams have collected more points than Luton over their last six Championship games, and we can see them recording another victory here.
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