Both nations are looking to make up for a disappointing summer, with Italy failing to qualify for the World Cup for the first time in 60 years and Poland finishing bottom of their group in Russia.
Roberto Mancini and Jerzy Brzeczek start their new career paths as national manager, with the former taking over the permanent post from Gian Piero Ventura and the latter from Adam Nawałka.
Ahead of Friday's evening, Goal takes a look at everything you need to know.
|Game||Italy vs Poland|
|Date||Friday, September 7|
|Time||7:45pm BST / 2:45pm ET|
TV Channel, Live Stream & How To Watch
In the United States (US) the game will be shown on ESPN2 and is available to stream live online using ESPN+.
|US TV channel||Online stream|
The game can be watched live on television in the United Kingdom (UK) via Sky Sports Football or Sky Sports Mix and it can be streamed live online using Sky Go.
|UK TV channel||Online stream|
|Sky Sports Football, Sky Sports Mix||Sky Go|
Squads & Team News
|Goalkeepers||Cragno, Donnarumma, Perin, Sirigu|
|Defenders||Biraghi, Lazzari, Bonucci, Rugani, Chiellini, Romagnoli, Caldara, Criscito, Zappacosta, Palmieri|
|Midfielders||Barella, Benassi, Cristante, Pellegrini, Zaniolo, Gagliardini, Jorginho|
|Forwards||Balotelli, Zaza, Belotti, Berardi, Bernardeschi, Bonaventura, Chiesa, Immobile, Insigne, Pellegri|
Mario Balotelli has been handed a place in the starting XI following his recall by Mancini, while Chelsea midfielder Jorginho will play in a central position in a 4-3-3.
Potential Italy XI: Donnarumma, Biraghi, Chiellini (C), Bonucci, Zappacosta, Pellegrini, Jorginho, Gagliardini, Bernardeschi, Insigne, Balotelli
|Goalkeepers||Fabianski, Skorupski, Szczesny|
|Defenders||Bednarek, Bereszynski, Dzwigala, Glik, Kaminski, Kedziora, Pietrzak, Reca, Rybus|
|Midfielders||Blaszczykowski, Frankowski, Goralski, Kadzior, Klich, Krychowiak, Kurzawa, Linetty, Makuszewski, Romanczuk, Szymanski, Zielinski|
|Forwards||Lewandowski, Milik, Piatek|
Kamil Glik returns to the team after missing two of Poland's three World Cup games.
Potential Poland XI: Fabianski, Bereszynski, Glik, Bednarek, Reca, Krychowiak, Klich, Kuba, Kurzawa, Zielinski, Lewandowski (C)
Betting & Match Odds
Italy are strong favourites to win the game and are priced at 4/6 by bet365, while Poland's chances of winning are rated 11/2. A draw between the teams is a 27/10 bet.
Friday offers the chance for a fresh start for the Italian national team following a difficult spell under the guidance of Ventura.
The Azzurri failed to qualify for the World Cup finals for the first time since 1958 and Ventura was ultimately sacked after 16 games in charge.
"It is my first game; we will start a new chapter with some new people," Mancini said ahead of the game.
"It will be interesting to play against Italy as both teams are in a similar situation. Poland did not do as well as people expected at the World Cup, and Italy – a giant of world football – did not qualify at all.
"Aside from final tournaments, I cannot remember Poland getting to play big teams as often [as in the Nations League]. It is a good test which will show immediately whether my choices are the right ones."
And while new boss Brzeczek is excited about the talent in his squad, the former midfielder is looking to use the upcoming internatonal break merely to get his players used to each other.
"We come into the UEFA Nations League convinced that we can do well and win games," he said.
"The first objective is to gel as a team, because only three or four players in the world can win games by themselves.
"Poland had a poor World Cup but are a great team. We have experienced players and youngsters who can add a lot, even if Italy tend to struggle to find space against big teams."