Against the best team in the world, Thomas Tuchel's defensive decisions will be key. And he has many to make.
The England head coach said before Croatia at Wembley on Thursday that he was quite happy to go full-strength in both matches, despite the three-day gap, and he was true to his word. All the big guns were out for Harry Kane's big night.
Barring unexpected late injury or illness, the best player in the world will lead the line against the world champions. Morgan Rogers should start at right wing, Anthony Gordon left wing. England's Madrid maestro Jude Bellingham will play No 10, and Elliot Anderson and Declan Rice will form the double-pivot at No 8.
But behind that, is where Tuchel and his assistant Anthony Barry will be pondering their options.
Do England have a new No 1?
The decision Tuchel makes about his goalkeeper could be one of the most important we have seen for eight years.
Since the World Cup of 2018 in Russia, Jordan Pickford's consistent brilliance has seen him largely unchallenged as England's first-choice keeper. Not so now.
As he nears his century of international caps (Pickford has 94) there is a new pretender to his throne, James Trafford. In the last international camp, Tuchel shared the four games out equally between the two and he has hinted he will do the same this time round.
Seeing Pickford walk out at Wembley on Thursday, in the lesser of the two matches, was a surprise. Most onlookers expected him to get the nod against the world champions in Madrid. He may yet do so. But if he doesn't, if Tuchel sticks to the plan he outlined at the start of the camp and brings Trafford in then it will feel like a real "changing of the guard" moment for the England No 1 shirt.
How to stop Lamine Yamal?
In terms of outfielders, no decision is bigger than who should play left-back, to try to combat the most potent of Spain's threats, Lamine Yamal. The man who finished third in the Ballon d'Or rankings stayed in Barcelona for treatment on a troublesome right knee rather than travelling to Prague on Thursday night. He was being saved for England and he is fit and back with the national team now.
Most likely, Lewis Hall will be given the task of keeping Lamine Yamal quiet, keeping his place on the left side of England's defence. Tuchel said after his performance against Croatia that Hall is "doing all he needs to do" to nail down the role as England's first choice and that he is playing "top level".
The Newcastle defender has already proved himself against Barcelona's wondrous winger. In the spring of this year, in the Champions League, he put in a performance that led the Spanish-based newspaper Mundo Deportivo to label Hall the "anti-Lamine".
On the other side of England's defence, it feels like a straight shoot-out between Ben White and Djed Spence, with Trent Alexander-Arnold no doubt expecting to be dropped. Tuchel has consistently questioned his defending and so he is likely to sit out the test in Spain.
Spence missed two England training sessions and Thursday night's game against Croatia as he nursed himself to be ready for this one. He was one of England's most formidable finds of the World Cup, proving himself to be the team's best one-on-one defender.
White has only started one game for his country since before the 2022 World Cup in Qatar and that was the 1-0 home defeat to Japan. If he does get the nod over Spence, both he and Tuchel will hope he avoids the boos which marked his substitute appearance against Croatia on Thursday night.
Alex Baena, who is likely to be Spain's left winger, doesn't pose the same threat as Lamine Yamal on the other flank but he did score against Czech Republic a few days ago - and against England at Wembley.
In the centre of England's defence, again, Tuchel has some big calls. If Ezri Konsa, rested against Croatia, is now fully fit, as he seems to be, he will almost certainly be recalled straight to the heart of the defence. In the absence of the injured Marc Guehi and John Stones he is England's most senior and most influential defender.
Jarell Quansah, who had a howler for Croatia's equalising goal, may well drop out because he is considered a right-sided centre-back, as is Konsa. So that would mean the left-leaning Dan Burn or Jarrad Branthwaite coming in alongside the Arsenal man. Best bet there is Burn.
A significant match for Tuchel's England 2.0
Significantly, Trafford was the preferred choice when Tuchel's men played Spain in September.
For that reason, and also because this is England's final game of 2026, and because it is their last until the Nations League quarter-finals in March - it feels a hugely significant match.
The animosity from large chunks of England's support, and from some England players, towards Tuchel for those now infamous tactical choices of the World Cup semi-final against Argentina, have melted away. The national team's autumn performances have reignited hope and belief.
Which way the result - and the performance - goes against the World Cup winners, will almost certainly dictate the mood and the direction of travel for England from here on in.
In the persistent rain of Madrid, the game will be a barometer of where England are, in project Thomas Tuchel 2.0.