Michael O'Neill will be looking to take his side to the finals for the first time since 1986, a tall order in itself, but O'Neill and his squad would appear to have the belief that this could finally be their time to shine on the biggest stage in world football.
Gattuso unhappy with play-off rule
Perhaps their confidence lies in the fact that all the pressure is on the Azzurri, who haven't qualified for the showpiece event since the 2014 edition in Brazil.
Italy manager, Gennaro Gattuso, certainly isn't happy about how things have panned out this time around.
"In my day, the best runners-up went straight to the World Cup. Now the rules have changed," he was quoted as saying in the lead-up to this game.
Given that his squad won all their games apart from the two against Norway, and Northern Ireland finished third in their group, having only won three games, one can understand Gattuso's frustrations.
Azzurri full of elite-level players
He knows all about the pressure of tournament football, of course, having been part of the 2006 World Cup-winning side.
His squad is full of players that have elite-level experience, so the likes of Sandro Tonali, who should be fit for this game, Mateo Retegui, Alessandro Bastoni, Nicolo Barella, Riccardo Calafiori, Gianluigi Donnarumma and others, will be expected to step up and ease the Italians to the next stage.
The winners will face either Wales or Bosnia-Herzegovina, and whoever triumphs in that game will find themselves in World Cup Group B, alongside Canada, Qatar and Switzerland.
In the last six head-to-heads, dating back to June 2003, the Azzurri have stopped Northern Ireland from even scoring a single goal.
Two goalless draws are the best it's got for the visitors during that period, and not since 1958 have they beaten Italy, so if they want to pull off one of the shocks of the playoffs, they can't allow the weight of history to hang too heavily on their shoulders.
Third time lucky?
Arguably, Italy also have to put recent failures to the back of their minds too. Eight years ago, it was Sweden that went to the World Cup at their expense.
Then, North Macedonia sent shockwaves through football four years ago when Aleksandar Trajkovski's 93rd-minute winner in Palermo knocked the Azzurri out at the semi-final stage of the playoffs.
"I've been coaching for a number of years now, but certainly this game is the most important fixture of my coaching career so far," Gattuso added, noting that he rarely sleeps before big games because the surge of adrenaline is just too much.
"I'm prepared and, believe me, I'm not thinking about things going badly, I'm thinking positively."
Northern Ireland are confident of an upset
For his part, O'Neill was equally as bullish.
"I have a lot of belief in this group of players, and it will be a young team that will take the field," he said.
"I think the benefits you get with youth is a lack of fear. We have everything to gain in the game, there's no doubt about that."
Northern Ireland will certainly have to up their game, as two of their three wins during qualifying came against lowly Luxembourg.
Italy, by contrast, hit eight in two games against Estonia, and eight more in their two games against Israel.
Retegui the dangerman
Keeping tabs on Retegui has to be one of the main focuses for Northern Ireland. The 26-year-old has not only scored the most goals for Italy in qualifying (five), but he also has the joint most assists (four), has taken the most shots (29) and has the most on target (10).
With Tonali creating the most chances (23), the visitors have their work cut out. Particularly when you realise that they have six joint top-scorers in qualifying - Jamie Reid, Jamie Donley, Trai Hume, Shea Charles, Isaac Price and Justin Devenney - but all have just a single goal.
22-year-old Price's 14 total shots and four on target is his side's best return, whilst Devenney is their creator supreme with nine.
With Italy having both scored their most goals (seven) and conceded their most (six) in the final 15 minutes of their qualifying matches, this game is likely to go the distance.
First goal is vital
The Northern Irish are actually at their most potent in front of goal in the 15 minutes leading into half-time, so as long as they're still in the game at that point, O'Neill has to urge them forward.
The first goal is vital for the visitors too, as if they get on the scoreboard before their hosts, they can point to a qualifying campaign where they haven't lost once they are in front.
Concede first, however, and they've not gone on to win.
Game on!
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