Spain suffered a surprise 1-0 loss to Ukraine last time out, while the hosts enter this fixture winless in four matches.
The Netherlands would have entered this year's European Championship finals among the favourites had they gone ahead as planned, but instead they are in a bit of a crisis.
Add the long-term absence of influential defender Virgil van Dijk to the mix and it is clear to see why the mood has been so low around the Dutch camp.
After losing 1-0 to Mexico in a friendly and drawing 0-0 with Bosnia-Herzegovina in a UEFA Nations League clash, Oranje did at least score their first goal under De Boer last time out.
De Boer's men find themselves third in Nations League Group A1, two points behind leaders Poland, whom they take on next week.
Before that is a home match with Bosnia-Herzegovina and this visit of Spain, who are also in need of a pick-me-up on the back of an underwhelming October.
One goal from three matches is a little worrying for La Roja and something Enrique will be looking to put right, starting with this trip to the Dutch capital.
Spain's priority will be the upcoming Nations League Group A4 games with Switzerland and Germany, however, with the 2010 World Cup winners one point clear at the top.
This will be the first meeting between the two European giants since a friendly five years ago, which Spain won 2-0.
Netherlands form (all competitions): WWLLDD
Spain form (all competitions): WDWDWL
Given his side's lack of goals of late, Enrique may opt to give Llorente - now used further forward - and Morata a chance to shine in Amsterdam.
As for the Netherlands, Ajax star Davy Klaassen is back involved and may earn his first cap since October 2017.
With the Nations League taking priority, this might be the game for certain fringe players to be given a run out.
Netherlands possible starting lineup:
Krul; Hateboer, De Vrij, Ake, Van Aanholt; Van de Beek, Klaassen, Wijnaldum; Berghuis, Depay, Babel
Spain possible starting lineup:
Kepa; Navas, Ramos, P.Torres, Gaya; Canales, Rodri, Merino; Olmo, Llorente; Morata
We say: Netherlands 1-1 Spain
Spain are in need of some momentum, having gone nearly a year since last winning back-to-back matches.
The Netherlands are in a similar position, seeking their first win under De Boer, and we can see both of those runs being prolonged in a score draw on Wednesday.