The two sides are adrift of table-topping Arsenal Under-21s and Colchester United, but with at least one of their rivals guaranteed to drop points, all four teams are still waiting to learn their fate.
Match preview
Sixteen years on from winning their first and only EFL Trophy to date in the 2007-08 edition, MK Dons are one dissatisfactory result away from falling at the first hurdle in this year's competition, where they are yet to win a match in 90 minutes.
During Mike Williamson's time at the helm, the Dons succumbed to a 2-1 defeat to Colchester in their opening battle, but they blew Group E wide open by beating Arsenal on penalties after a 2-2 draw on matchday two under Scott Lindsey, thereby earning the precious bonus point for winning the 12-yard shootout.
A stalemate and penalty success may not suffice for MK Dons this time around, though - they will likely need a victory on Tuesday will give them a fighting chance of qualifying for the last 32 - and even that may not be enough if Arsenal and Colchester play out a draw in 90 minutes.
The hosts' fate therefore lies out of their own hands, and they have already experienced one dose of knockout misery this month, being defeated 2-0 at home to AFC Wimbledon in their FA Cup first-round grudge match, but League Two has been going swimmingly.
Indeed, Lindsey's men made it four straight victories in the fourth tier with a 3-1 triumph over Swindon Town on Saturday, taking them into the playoff positions in sixth place in the League Two table, only three points below Walsall in the runners-up spot.
Sharing MK Dons' fate in terms of results, Colchester also opened their EFL Trophy campaign with a 2-1 defeat before atoning for their errors from the penalty spot at the second time of asking, firstly being gunned down by Arsenal's young guns in September.
Orient managed to right those wrongs when Colchester came to visit last month - prevailing 4-2 on penalties following a 1-1 stalemate in 90 minutes - but they could have had a three-point haul rather than two had they not shipped a 79th-minute equaliser to the League Two side.
As is the case with Tuesday's hosts, Leyton Orient's destiny will be decided elsewhere regardless of their result at Stadium mk, but Richie Wellens's men have slowly been rediscovering that winning feeling, coming up trumps in three of their last four games in all tournaments.
That sequence includes another penalty-shootout triumph over Boreham Wood in the first round of the FA Cup, and a ruthless 3-0 beating of Blackpool in Saturday's League One affair, one that boosted their survival prospects as they sit 20th in the standings.
The League One survival fight will no doubt take precedence over a possible EFL Trophy triumph for Leyton Orient, who have been defeated in each of their last three matches against MK Dons, most recently in an EFL Trophy penalty shootout in 2021.
MK Dons EFL Trophy form:
L
W
MK Dons form (all competitions):
L
W
W
W
L
W
Leyton Orient EFL Trophy form:
L
W
Leyton Orient form (all competitions):
W
L
W
L
W
W
Team News
MK Dons do not have to concern themselves with any cup-tied players, international call-ups or suspensions this week, and the hosts will also have Connor Lemonheigh-Evans back from a ban, having missed the Swindon win after being dismissed against Wimbledon in the cup.
Midfielder Liam Kelly is recovering from the hamstring issue he sustained against Grimsby Town last month, though, while Tom Carroll and Nico Lawrence are no closer to returning either.
On a brighter note, Callum Hendry came through 35 minutes of the Swindon victory unscathed and may now come into contention for a starting role, and a 914th appearance could be in store for Dons legend Dean Lewington.
Leyton Orient do have one player on the naughty step this week, though, as centre-back Jack Simpson picked up his second booking of the EFL Trophy in the win over Colchester and will therefore serve a one-match competition ban on Tuesday.
Twenty-three-year-old midfielder Ethan Galbraith has also been called up to the Northern Ireland senior team; his absence could open the door for Tottenham Hotspur-owned Jamie Donley to start just behind the striker.
Theo Archibald and Jordan Graham are also still recuperating from long-term injury problems, but Jayden Sweeney is back in contention after serving a suspension for his sending-off against Boreham Wood.
MK Dons possible starting lineup:
MacGillivray; Maguire, Williams, Lewington; Pritchard, Lemonheigh-Evans, White, Ilunga; Leigh, Hendry; Harrison
Leyton Orient possible starting lineup:
Phillips; Ball, Beckles, Happe, Sweeney; Obiero, Warrington; Perkins, Donley, Jaiyesimi; Kelman
We say: MK Dons 1-1 Leyton Orient (Leyton Orient win on penalties)
With MK Dons flying high in League Two and Leyton Orient at risk of demotion from League One, Tuesday's encounter is a difficult game to call, especially with both sides also on cloud nine from dominant wins at the weekend.