The last time this pair met was in a dramatic clash in October, as they fought it out for a place in the World Cup play-offs. James McClean scored the only goal of the game to give the Irish a win, and secure a top two finish.
The two are not in the best of form, as both sides have one win from their last five encounters in all competitions. However, the hosts have home advantage in addition to having a more experienced squad.
Wales will be relying on the services of Real Madrid forward Gareth Bale whilst Ryan Giggs has replaced Chris Coleman since their last encounter.
This will be their first ever UEFA Nations League game, but can the Irish repeat their victory in Cardiff?
Wales scored a single goal in four of their last five home friendlies while the Republic of Ireland have seen Under 2.5 Goals in their last five away matches. Backing Under 2.5 Goals looks very promising and you can get odds of 1.35 here.
Both Teams to Score No has been witnessed in the last five head to head encounters between the two sides. Ireland have also failed to score in three of their last five fixtures, making Both Teams to Score extremely attractive at odds of 1.50 here.
The Irish have lost three of their last four, including back to back away trips and they have a considerably weaker squad having called up a good number of championship stars. Wales have called up a good number of their best stars with Bale leading the pack and we think there is value in backing Home Win at odd of 1.90.
Wales will be without Hal Robson-Kanu who announced his retirement from international duty recently. The Welsh have added 19-year-old Tyler Roberts in to their squad, and he's fighting for his first cap here.
Harry Arter dropped out after a rumoured bust-up with Roy Keane, while McClean has withdrawn from the squad through injury. He is joined by Shane Long.
Probable line ups
Wales: Hennessey, Gunter, Chester, Williams, Davies, King, Allen, Bale, Ramsey, Lawrence, Vokes
Republic of Ireland: Randolph, Coleman, Duffy, Long, Ward, Doherty, Hendrick, Meyler, Browne, O’Dowda, Walters.