The Blues face the Premier League side’s young guns at Fratton Park in their final group game of this season’s competition.
And although Pompey haven’t won a game yet in this year's event – suffering defeats to both AFC Winbledon and Sutton United – they can still qualify for the next stage.
Here’s all the permutations and everything you need to know heading into tonight’s game.
A must win game
Tonight’s fixture is a must-win one for Danny Cowley’s side if they are to stand any chance of reaching the next round.
Crystal Palace under-21s have won one and lost one as they sit joint-second in the group alongside AFC Wimbledon with three points.
But both can still be caught for Pompey to claim second place in Southern Group B.
How can Pompey qualify?
Pompey currently sit bottom of Southern Group B following two losses.
They have zero points, a goal difference of minus four and sit three points off joint-second AFC Wimbledon and Crystal Palace U21s.
Sutton are top with six points from their two games played.
And if the U’s beat Wimbledon tonight at Gander Green Lane, then the Blues stand a chance of progressing.
However, they could have to beat the young Eagles by at least three clear goals – something Sutton achieved in their opening Papa John’s Trophy game of the season.
Predicted team news
Cowley is expected to give fringe players and youth a chance against Palace.
That’s because injuries continue to mount up at Fratton Park, while Gavin Bazunu and Joe Morrell are both away on international duty.
Expect Harvey Hughes to be given a run-out at left-back, while Izzy Kaba and Harry Jewitt-White are likely to be involved at some point.
Yet, don’t be surprised if Cowley hands some of his regulars a game as he looks to build confidence and momentum.
When was the last time Pompey failed to qualify for the knockout stages of the Trophy?
The last time the Blues failed to qualify for the knockout stages of the EFL Trophy was during the 2016-17 season under former boss Paul Cook.
That campaign saw Yeovil and Reading qualify for the knockouts ahead of Cook’s side, who only managed one victory in that year's competition.
Following Cook’s departure, his replacement, Kenny Jackett, qualified every season during his tenure.
Indeed, his Blues side reached the final in consecutive years, winning it in 2019 by beating Sunderland in a penalty shootout.
They lost to Salford in March earlier this year – a result which cost Jackett his job.
Who could Pompey face IF they win tonight and progress?
Cowley’s side can only finish second in the group if they win tonight and the result at Sutton goes their way.
Round two remains split regionally into northern and southern sections, with group winners drawn at home against a runner-up from another group.
This means if Cowley’s side qualify they will play away from Fratton Park in the second round.
When is the second round draw?
With the final round of group fixtures taking place tomorrow night, the groups will then be set for the second-round draw.
The draw will take place following Port Vale’s League Two game against Bradford – which us being shown live on Sky Sports – on Saturday.
Kick-off is at midday.
Round two ties will be played week commencing November 29.
Which teams have already qualified and who can still qualify?
Qualified Northern: Hartlepool United, Carlisle United, Tranmere Rovers, Crewe Alexandra, Bolton Wanderers, Rotherham United, Lincoln City, Sunderland, Fleetwood Town, Accrington Stanley, Sheffield Wednesday and Harrogate Town.
Can still qualify (Northern): Oldham Athletic, Salford City, Shrewsbury Town, Wolves U21, Wigan Athletic, Rochdale, Port Vale, Liverpool U21, Man City U21, Doncaster Rovers and Scunthorpe United.
Qualified Southern: West Ham U21, Aston Villa U21, MK Dons, Walsall, Chelsea U21, Swindon Town, Charlton Athletic, Leyton Orient and Cambridge United.
Can still qualify (Southern): Ipswich Town, Colchester United, Sutton United, AFC Wimbledon, Crystal Palace U21, POMPEY, Brighton U21, Forest Green Rovers, Bristol Rovers, Exeter City, Arsenal U21, Newport County, Stevenage and Spurs U21.