Just two points separated the sides at the end of the regular campaign and both teams upset the odds to advance through tough semi-final ties, but something has to give this weekend.
Newport's dream of promotion to the third tier of English football for the first time in more than three decades would not have been possible had it not been for a late Jamille Matt goal on the final day of the regular campaign.
Matt found a way through three minutes from time to snatch County a 1-1 draw with Morecambe, proving enough to finish a point above Colchester United, Exeter City and Stevenage in the final playoff spot.
Then came a two-legged semi-final with promotion favourites Mansfield Town. Newport once again struck late in the home leg to earn a 1-1 draw, before then beating the Stags on penalties after a goalless but eventful return match at Field Mill.
The bookies have Newport down as the underdogs for Saturday's match - an assessment that Michael Flynn agrees with given that Tranmere finished one place better off after 46 regular-season fixtures.
County have been in terrific form, however, having gone 12 matches since their last defeat - 1-0 to Northampton Town in mid-March.
That loss left Flynn's men 13th in the table, eight points behind seventh-placed Colchester with just 10 games to play.
Twenty-two points from a possible 30 to see out the campaign proved to be enough to get Newport over the line, and now they will feel that momentum is on their side ahead of this massive showdown at Wembley.
County will certainly not be fazed by playing at the home of English football as they have already played there a few times in the last seven years.
As well as losing the 2012 FA Trophy final to York City and an FA Cup replay away to Tottenham Hotspur last year, County also earned promotion from the National League there in 2013.
That was the Welsh side's happiest day since reforming in 1989, securing promotion thanks to a 2-0 win over Wrexham, and they are now on course to make it to within two promotions of the Premier League - a journey that would not have been possible if not for the work of impressive manager Flynn.
Recent form in League Two (including playoffs): DWWDDW
Tranmere ended the regular season with just one win from their final seven matches, culminating in a 3-1 loss at Crawley Town on the last day of the campaign.
With a playoff place already secured, however, Micky Mellon was given the luxury of being allowed to make eight changes to his starting lineup for that trip to Broadfield Stadium.
That paid off in the playoff semi-finals as Mellon's side beat Forest Green Rovers 1-0 in the first leg through a stunning Ollie Banks strike - 10 minutes after Gavin Gunning was dismissed for the visitors - before completing the job with a 1-1 draw in the return match.
Rovers are now within one win of joining the rare breed of clubs to have won back-to-back promotions, having overcome Boreham Wood a little over 12 months ago to escape the National League.
It is the third year in a row that Mellon's men have made it to Wembley, as they narrowly missed out on promotion in 2017 with defeat to, of all sides, Forest Green.
Tranmere are now bidding to return to League One for the first time since being relegated in 2014, which was followed by another demotion and a few years languishing in non-league.
While Newport have had two goalscorers in their ranks this term - Padraig Amond and Matt - Rovers have the highest-scoring player in English football this term, with James Norwood netting 32 times in all competitions, including a key goal against Forest Green last time out.
Participating in their first Football League playoff final since 1991, when they beat Bolton Wanderers at Wembley in the third-tier final, Tranmere now have the chance to complete their five-year journey back to League One. Going by the past couple of years, you would not bet against them achieving exactly that this weekend.
Recent form in League Two (including playoffs): LDDLWD
Flynn has no injury and suspension concerns for this match, giving him a full selection of players to choose from.
County switched to a four-man backline against Mansfield last week, after using a 3-5-2 formation throughout the season, but Flynn is expected to revert back to default on Saturday.
After rotating his side for the final game of the regular campaign, meanwhile, Mellon stuck with the same XI for both legs of the playoff semi-finals against Forest Green.
In the continued absence of key man Luke McCullough, Mellon is expected to once again go with the same side for this massive match.
Norwood has scored 30 goals in League Two this season, including the playoffs, to become the first player to reach that tally since 2012-13 (Tom Pope for Port Vale, 31). Norwood scored the winner for Rovers in last season's National League playoff final and will be the first name on the teamsheet here.
Newport possible starting lineup:
Day; Poole, O'Brien, Demetriou; Willmott, Dolan, Bennett, Sheehan, Butler; Matt, Amond
Tranmere possible starting lineup:
Davies; Caprice, Nelson, Monthe, Ridehalgh; Morris, Harris, Banks, Perkins, Jennings; Norwood
Head To Head
Newport are unbeaten in four Football League meetings with Tranmere, with their last defeat against Rovers coming in April 1988.
This is the first League Two playoff final between the sides finishing sixth and seventh since 2012-13, when seventh-placed Bradford City won 3-0 against Northampton Town.
We say: Newport 2-1 Tranmere
The side finishing seventh has been promoted via the League Two playoffs in four of the previous seven seasons. Newport have momentum on their side thanks to a strong end to the campaign, in stark contrast to their opponents, and we are backing them to earn a place in the third tier of English football for the first time since 1987.