Frenkie De Jong produced a masterclass to help Holland defeat Wales and then delivered a blow to Manchester United too.
Holland were a class apart in Rotterdam early on as they aimed to make it 10 wins from 10 games against Wales.
Barcelona ’s Manchester United target De Jong, who used to play under Erik ten Hag at Ajax, impressed in holding midfield with his calmness on the ball and wide passing range.
He helped the hosts race into a 2-0 lead with early goals from Noa Lang and Cody Gakpo.
But Brennan Johnson scored a beauty to halve the deficit before the break in Wales’ final game of five matches in 14 days.
Sub captain Gareth Bale then looked to have levelled the Nations League tie with a stoppage time leveller from the spot.
But there was still time for Memphis Depay to bury a winner as Holland triumphed in dramatic fashion just as they did in Cardiff last week when Wales also equalised late on.
Wales boss Rob Page described playmaker De Jong as "phenomenal" and afterwards the £70million-rated ace, 25, was asked about his future amid links to Old Trafford to play under his former coach.
De Jong replied: “You are always flattered when teams show interest in you as a player.
“But I think I am at the biggest club in the world at the moment and feel fine there so there is no news.”
While United digest another potential blow in the transfer market after Darwin Nunez’s switch to Liverpool, Wales must address conceding so quickly after scoring.
This was a further lesson for boss Page and his squad ahead of the winter’s World Cup.
Skipper Bale reflected: "It's hard to take but I'd rather this happen now and we address it than it happen at the World Cup.
"We have to use these Nations League games to improve and get better.
"I was saying in the changing room, we're in League A playing against big teams, of course we are disappointed we conceded late, but we're competing with these big teams in every game now and it's just the finer details we need to iron out.
"If we can do that it will put us in a good place for the World Cup."
There was a nice touch from the Dutch crowd as they applauded Wales' qualification for the 2022 World Cup before the game.
But the hosts showed Wales no quarter once the contest started and they went on the attack with Bale and Aaron Ramsey starting on the bench.
The visitors fell behind when Wes Burns lost the ball on their left touchline attempting to chop back inside.
Vincent Janssen found Lang who twisted and turned before firing a fine low shot past Wayne Hennessey in the 17th minute.Holland doubled their lead in the 23rd minute as Gakpo had a shot blocked but the ball fell kindly to him to bury his next finish into the corner.
Just three minutes later Wales pulled a goal back after Dan James won the ball high up the pitch before Harry Wilson found Johnson.
The Nottingham Forest ace produced a brilliant first-time low right-foot finish into the far corner from the top of the box for his second international goal in four days.
Wales then looked to have snatched a draw when they won a late penalty after Connor Roberts was fouled by Tyrell Malacia as Bale converted his penalty low into the bottom corner for his 39th international goal.
But there was still time for Dutch sub Memphis Depay to score to break Wales' hearts.
