Both sides have a good history in progressing from this stage of the competition, with the home side reaching the second round in 13 of their last 14 campaigns, while the away side have advanced in seven of their last eight.
Match preview
Carlisle have built on their 20th-placed finish last season, currently occupying seventh place in League Two, just inside the playoff positions.
The Blues were undefeated in September, picking up a good 2-1 win away at Grimsby Town and defeating AFC Wimbledon by the same scoreline at home, but mainly they were just hard to beat, drawing three of their five games that month.
Form really started to pick up after that, as Paul Simpson's side recorded two wins on the spin, defeating Hartlepool United 3-1 and Doncaster Rovers 3-0 in successive games, leaving them three points off the automatic promotion places with a game in hand at their disposal.
However, defeats against first-placed Leyton Orient and a Stockport County side in good form followed, with Simpson's men unable to make up ground on the top three.
That was until last week, when Krystian Dennis got back to his familiar self in a trip to Tranmere, bagging a brace in a 2-0 victory, which will undoubtedly boost confidence heading into a game against the same opponents one week later.
Indeed, the Rovers were not up to the task against the Blues last week, and Micky Mellon will be hoping that they can put an end to what is now a four-game winless run.
Heading into an away trip to Harrogate Town near the end of October, expectations were high for the Wirral club, having won their last five league games without conceding a goal, although they had to settle for a point at a side contending with the threat of relegation.
That result commenced a poor run of form for Tranmere, who missed an opportunity to push for the playoffs, which they are now two points shy of, and they have also played a game more than the four teams immediately above them.
While Carlisle had a rest in the week, Mellon's men welcomed Stockport County to Prenton Park in what was the first competitive meeting between the two clubs since a League One clash in 2010.
Both sides had chances, with Paul Lewis going agonisingly close to putting the Rovers in front just minutes after being brought on in the second half, but the spoils were shared, in a result that is likely to suit Stockport more than Tranmere.
Carlisle United form (all competitions):
W
W
L
L
L
W
Tranmere Rovers form (all competitions):
W
W
D
D
L
D
Team News
Carlisle striker Krystian Dennis got the job done at Prenton Park, and he will in all likelihood lead the line for his side again, having scored nine league goals this season, the joint-third highest figure in League Two.
Set to accompany him in attack is Jack Stretton after the 21-year-old played the full 90 minutes last weekend, also scoring a brace recently against Doncaster Rovers.
Following a three-game winless run, Tranmere manager Mellon opted for a change of system against Stockport on Tuesday, bringing Kyle Jameson into the defence, a move that meant Josh Hawkes was sacrificed on the wing.
Despite not winning, the Rovers showed some promising signs in the match, and in all likelihood the man in charge will stick with the new system, having already came up short against Carlisle playing 4-4-2.
Elliott Nevitt may drop to the bench, with the striker not scoring in his last four matches and being withdrawn early for Paul Lewis on Tuesday night, who may start in his place.
Carlisle United possible starting lineup:
Holy; Ellis, Huntington, Feeney, Mellish, Armer; Moxon, Guy, Charters; Dennis, Stretton
Tranmere Rovers possible starting lineup:
Doohan; Simeu, Turnbull, Jameson; Dacres-Cogley, Morris, O'Connor, Merrie, Bristow; Lewis, Hemmings
We say: Carlisle United 2-0 Tranmere Rovers
Carlisle cruised to victory at Prenton Park last week, and they should have no trouble doing the same again on home turf. We expect the Blues to repeat the scoreline from last week and book their place in the next round.