Although the Dragons will be satisfied with their World Cup spot, they require a result against a Belgium side who have just hit six past Poland.
Match preview
Having matched the highs that they achieved during Euro 2016 with qualification for the World Cup, it was always going to be a big ask for Wales to collect a result against the Netherlands on Wednesday.
To the credit of Rob Page and his team, they came within seconds of earning a hugely credible result in Cardiff, equalising through Rhys Norrington-Davies in the 92nd minute.
However, the visitors went straight up the other end, Wout Weghorst netting the decisive goal to earn his team a 2-1 win and condemn Wales to their second successive Nations League setback.
With Belgium and the reverse fixture with Netherlands still to come before June 14, no-one would be quick to criticise Wales if they continue to fall short, a five-match period over two weeks a brutal end to an already-exhausting campaign.
Nevertheless, Page will want to ensure that their stint in the top tier in this competition is not a brief one, heaping the pressure on at least a draw being recorded against their familiar foes.
Since September 2012, these two teams have met on seven occasions, playing each other in three qualification campaigns and that famous Euro 2016 quarter-final.
Wales have more than held their own - only losing one of the last six games - but Roberto Martinez's side seemingly have an extra edge about them having been trounced 4-1 at home to the Netherlands last week.
In response, Belgium came from behind to put six goals past Poland on Wednesday, the demolition occurring in the absence of the injured Romelu Lukaku.
The Red Devils still sit three points adrift of group leaders Netherlands, although they will certainly have a spring in their step when they take to the pitch in Cardiff.
Belgium are also closing in on scoring in every fixture over a four-year period, the last time that they drew a blank coming against France in the 2018 World Cup semi-finals.
Wales Nations League form:
Wales form (all competitions):
Belgium Nations League form:
Belgium form (all competitions):
Team News
Gareth Bale will be among the Wales regulars to return to the starting lineup after being rested in midweek.
Ethan Ampadu, Neco Williams, Joe Allen, Aaron Ramsey and Kieffer Moore should also feature, but Page has issues with regards to the fitness of his goalkeepers.
Adam Davies is on standby if Wayne Hennessey does not shake off a knock, while Danny Ward is expected to miss out with a knee issue.
As for Belgium, Lukaku remains absent with the ankle injury that he sustained during the defeat to the Netherlands.
With a trip to Poland still to come, Martinez will make alterations to his starting lineup with Leandro Trossard, Thorgan Hazard and Dries Mertens potentially forming the front three.
Dedryck Boyata stands to earn an appearance in defence, possibly ahead of Jan Vertonghen, while there is scope for Leander Dendoncker moving further forward to hand a rest to Youri Tielemans.
Wales possible starting lineup:
Davies; Ampadu, Rodon, Davies; Williams, Morrell, Allen, Norrington-Davies; Ramsey; Bale, Moore
Belgium possible starting lineup:
Mignolet; Faes, Alderweireld, Boyata; Castagne, Dendoncker, Witsel, Carrasco; Trossard, Mertens, T.Hazard
We say: Wales 1-2 Belgium
With Wales likely to go as full-strength as possible, they should have enough quality to push their stronger opponents all of the way. However, this game could go a similar way to the one against the Netherlands, with Belgium potentially edging the contest in the closing stages.