Here, Press Association Sport considers some of the talking points surrounding Wales’ first game at the Principality Stadium since 2011.
Will Gareth Bale play?
The build-up to the first Wales-Spain fixture for 33 years has been dominated by the fitness of Gareth Bale. The Real Madrid star will be presented with a Golden Boot before kick-off to mark his record 30 goals for Wales but it remains to be seen whether he will feature against the country where he earns his living.
Bale is desperate to play after a groin problem which has reduced his playing time for Real in recent weeks, but he could sit this one out with an important Nations League date in the Republic of Ireland on Tuesday.
Wales’ last game at the Principality Stadium, the 74,500-capacity home of Welsh rugby, was in March 2011 – a 2-0 European Championship qualifying defeat to England. Since then Wales have enjoyed huge success down the road at the Cardiff City Stadium, a popular base for players and supporters alike.
The Football Association of Wales, however, have been keen to maximise financial opportunities by returning to the Principality Stadium for high-profile games. The move has angered some die-hard Welsh football fans, but an expected crowd of around 50,000 should make the decision worthwhile.
Skipper under scrutiny
Ashley Williams’ role in the Wales set-up continues to provoke debate. The veteran defender was omitted for last month’s Nations League defeat in Denmark after starting in the 4-1 win over the Republic three days earlier, with Bale taking over the captaincy in Aarhus.
It is evident Williams is not the commanding figure he once was, but manager Ryan Giggs has been steadfast in his conviction that Wales need the 34-year-old’s experience and leadership. Williams has had an upturn in form in recent weeks at Stoke, but whether he can cope with the pace of two international games in five days is another matter.
Exciting young guns
With Giggs at the Wales helm, comparisons between the current crop of Welsh youngsters and Manchester United’s celebrated ‘Class of 92’ have come thick and fast. The young Dragons have a long way to go before reaching the lofty standards Giggs and company managed at Old Trafford, but the signs are promising.
David Brooks has hit the Premier League ground running at Bournemouth while Connor Roberts, Chris Mepham and Harry Wilson are progressing at a rate of knots. Ethan Ampadu, the jewel in the crown, has yet to play for Chelsea this season but the 18-year-old showed against the Republic last month just how talented he is.
Spain won 2-1 at Wembley last month and welcome England to Seville for the Nations League return on Monday. Former Barcelona boss Luis Enrique is likely to rotate his squad as much as his players circulate the ball, but it does not really matter with so much talent at his disposal.
Isco, Dani Carvajal, Jordi Alba and Diego Costa might be missing this time. But David de Gea, Sergio Ramos, Sergio Busquets, Thiago Alcantara and Alvaro Morata provide plenty of stardust, and Spain appear back to their best after crushing World Cup finalists Croatia 6-0 last time out.