The Cobblers' promotion to League One will be confirmed if they pick up all three points, or if Stockport County fail to beat Hartlepool United at home.
It has been a very disappointing campaign for Tranmere, currently sitting in 11th place, 17 points behind the top seven, meaning they have nothing to play for in the final game of the season.
Recent form has been very unimpressive, with the Rovers winning just two of their last 11 games, despite the fact they have taken on a number of teams in the bottom half of the League Two table.
Ian Dawes has been in charge on an interim basis for the last eight games, after the sacking of Micky Mellon in early March, and despite a poor record as manager, the 39-year-old has been given the job full-time.
That decision has certainly been controversial among the Tranmere fans, but it may give the players some extra motivation to impress the new boss on Monday, as they look to earn themselves contracts for the 2023-24 campaign.
However, the Rovers have a very poor recent record against Monday's opponents, winless in the last six matches between the two sides, although they did manage to hold them to a point courtesy of a 0-0 draw in the reverse fixture earlier this season.
Northampton were hoping to have their promotion to League One wrapped up last weekend, but they fell to a 2-1 defeat at home against Bradford City, with Romoney Crichlow firing home a 94th-minute winner for the Bantams.
Not only did failing to win the match mean the Cobblers were unable to seal promotion back to the third tier, but that late goal means they know they must win at Prenton Park, whereas a draw would have been good enough if they held onto a point against Bradford.
Of course, Jon Brady's side could be promoted if Stockport fail to win, but given that the Hatters are playing already-relegated Hartlepool at home, that scenario is very unlikely.
With just two losses in their last 14 League Two games, Northampton have performed at the business end of the season, and they now need to hold their nerve for just one more game to return to the third tier for the first time since the 2020-21 campaign.
The Cobblers are no strangers to final-day heartbreak, having been denied promotion last season courtesy of Bristol Rovers winning 7-0 against Scunthorpe United, and they will be desperate to get over the line this time around.
With nothing left to play for this season, Dawes may use this game to bed in some young players, and striker Sam Taylor could get the nod in attack, having scored his first goal for Tranmere against AFC Wimbledon last time out.
Northampton manager Brady is likely to stick with a tried-and-tested for this crucial game, with top scorer Sam Hoskins set to keep his place at right-wing, looking to add to his 21 goals so far this season.
Max Dyche has forced his way into the side in recent weeks, scoring his first goal for the Cobblers last weekend, and the centre-back is set to keep his place in the side, partnering Sam Sherring at the back, in what should be a 4-3-3 system.
Tranmere Rovers possible starting lineup:
Hewelt; Cogley, Davies, Turnbull, Bristow; Hendry, Hughes, Turner-Cooke, Hawkes; Hemmings, Taylor
Northampton Town possible starting lineup:
Burge; Sherring, Dyche, Haynes, McWilliams; Honderman, Leonard, Bowie; Appere, Pinnock, Hoskins
We say: Tranmere Rovers 0-2 Northampton Town
Tranmere have been very disappointing all season, most recently drawing 1-1 away at 21st-placed AFC Wimbledon, and Dawes has not performed well in the role of interim manager.
As such, we expect the visitors to get over the line and secure promotion back to the third tier with a relatively comfortable victory.
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