World Cup winners France, Eden Hazard's Belgium and a fast-improving Netherlands under Ronald Koeman could all book places in the finals of the Nations League in matches between Thursday and Tuesday.
The competition, UEFA's bid to move away from meaningless friendly matches, has divided opinion in its inaugural season.
The strongest sides will qualify for the finals next June, but all 16 group winners will get a place in the Euro 2020 qualification playoffs.
However, if those nations have already qualified for Euro 2020 through normal qualifying, the best-ranked team from a lower group will be drafted in.
Qualifying for Euro 2020 does not begin until next March.
France on brink of qualification
Kylian Mbappe can carry world champions France into the finals on Friday with a draw against the resurgent Netherlands in Rotterdam.
"We are going there for the win," coach Didier Deschamps warned.
"We are the world champions and we will behave like it."
France beat the Dutch 2-1 in September after PSG star Mbappe scored the opener and Chelsea target man Olivier Giroud clinched the three points after Ryan Babel had equalised.
Since then the Netherlands have thrashed Germany 3-0 and drew 1-1 in Belgium.
Koeman is rebuilding the Dutch squad that failed to reach this year's World Cup with rookie striker Arnaut Groeneveld, a 21-year-old Nigerian-born winger, and Justin Kluivert, son of Patrick, two exciting new faces.
Two of the world's best defenders also go head-to-head as Real Madrid's Ballon d'Or contender Rafael Varane will line up for France and Liverpool's blockbuster signing, Dutch captain Virgil van Dijk, will marshall his backline.
Deschamps will be missing stars Paul Pogba and Benjamin Mendy but has recalled Moussa Sissoko, the versatile Tottenham man who was one of their stars in their run to the Euro 2016 final.
Not the Germany of old
Germany have struggled to put a disastrous World Cup behind them and face the prospect of relegation from Group A1 having taken a solitary point so far.
They have to beat the Netherlands in Gelsenkirchen on Monday to avoid dropping down a division.
Few observers expect Germany to fail to book their ticket to Euro 2020 through the normal qualifying process, but their form has done nothing to boost their flagging morale.
Coach Joachim Loew, who retained his job despite the first-round World Cup exit, has begun to dispense with the 2014 World Cup-winning players including Jerome Boateng and bring in fresh blood like Manchester City's Leroy Sane.
The incentive for the Dutch is clear: two wins will see them into next year's finals.
Belgium keeping form
Hazard's Belgium, the side that were only stopped at the World Cup by France, will reach the finals with a Group A2 win against Switzerland in Lucerne on Sunday. In fact, a draw would be enough if the Belgians avoid defeat against Iceland on Thursday.
Croatia seek revenge on Spain
World Cup finalists Croatia are hunting a first Nations League win when they host Spain, with revenge foremost in their minds after losing 6-0 to them in September.
"We are in much better shape than then. It was a debacle and we need to look for revenge... with three points," their coach Zlatko Dalic said.
The goalless Group A4 draw against England was played behind closed doors, so the game in Zagreb will be the first time Luka Modric has run out in front of a home crowd since inspiring Croatia to the World Cup final, a feat that makes him favourite to win the Ballon d'Or next month.
After a superb year that also landed him the FIFA player of the year award, the Real Madrid midfielder is nearing full fitness, Dalic said.
"He is the leader and he will be at a high level," the coach said.
Love it or loathe it
Liverpool's Jurgen Klopp calls the Nations League a "senseless" competition comparable to making a prize heavyweight box every night.
But Germany's Loew likes it, saying: "Competition is preferable to playing against small nations."