The League Two strugglers meet at Prenton Park, needing a win to boost their hopes of reaching the knockout phase.
Match preview
Having started their latest EFL Trophy campaign with defeat to Everton Under-21s back in August, losing 3-1 to their neighbours on home soil, Tranmere Rovers have some catching up to do in Group A.
Stockport County and Everton's youngsters lead the way with six and three points respectively, though Rovers and Accrington both have one game in hand - only the top two will qualify for this season's knockout stages.
Since that opening-day setback, Tranmere have showed few signs of progress in League Two, following last term's mid-table finish.
On Saturday, the Birkenhead club arrived in Milton Keynes without a win in four games, and it took a late leveller to secure a 1-1 draw against their hosts, MK Dons.
One minute into added time, Regan Hendry fired home from inside the box, moving his side onto a modest tally of 11 points, which is enough to occupy 17th place in the table.
For all their travails, Rovers have still lost just two league games this season - and none at Prenton Park - with several draws coming as a result of being the division's lowest scorers, with just five goals in nine matches so far.
Tranmere did notch three times in August's EFL Cup win over Accrington Stanley, though, with Omari Patrick's late goal applying the finishing touch to a comfortable 3-0 victory.
Accrington were then beaten 4-1 in their other cup contest this season, losing to EFL Trophy rivals Stockport on home turf at the start of September.
In League Two, John Doolan's strugglers trail Tranmere by five points, but they have just celebrated their long-awaited first win, beating Morecambe in a Lancashire derby at the Wham Stadium.
Dara Costelloe scored twice during the first half in a 2-1 success, and after Stanley had conceded late goals in all of their previous home games to drop points, this time they held on until the final whistle.
Both sides remain inside the relegation zone, but at least some pressure has been relieved on Doolan and co, who must tackle high-flying Gillingham at the weekend.
Tranmere Rovers EFL Trophy form:
L
Tranmere Rovers form (all competitions):
W
L
L
D
D
D
Accrington Stanley EFL Trophy form:
L
Accrington Stanley form (all competitions):
L
L
L
D
L
W
Team News
Nigel Adkins is set to rotate his Tranmere team on Tuesday evening, with several players returning to fitness hoping for inclusion in the hosts' squad.
Adkins has hailed the recent return of experienced striker Kristian Dennis, who scored against Swindon Town last week, but Josh Davison and Harvey Saunders may be promoted to the starting XI.
For Accrington's opening EFL Trophy contest, John Doolan made no fewer than nine changes, and he is expected to switch things up again, with an upcoming league game against Gillingham taking top priority.
Stanley hope to welcome back Jake Batty from a concussion that ruled him out of Saturday's home win, which would leave Doolan with a full squad to choose from. However, the Blackburn Rovers loanee may be preserved for the weekend.
Tranmere Rovers possible starting lineup:
McGee; Lee, Davies, Turnbull; Norman, Khan, Hendry, Bradshaw; Patrick, Davison, Saunders
Accrington Stanley possible starting lineup:
Kelly; O'Brien, Rawson, Awe, Pickles, Love; Whalley, Henderson, B. Woods, Costelloe; Knowles
We say: Tranmere Rovers 2-0 Accrington Stanley
Before the weekend, Accrington's previous win came against Tranmere at the end of April, and Stanley's defence have still not kept a clean sheet in 16 matches.