Having run out 1-0 winners when these sides last met in a friendly last year, they are 7/5 (2.40) favourites with bet365 to come out on top in Guimaraes.
However, Ronald Koeman's side will be in confident spirits after surprisingly seeing off France and Germany in the group stage, and can be backed at 19/10 (2.90) to go all the way to the final with a victory here.
Four of the last seven encounters between this pair have resulted in draws, and you can get odds of 9/4 (3.25) on this one heading into extra-time after another deadlocked 90 minutes.
Similarly, the likes of Jordan Henderson, Trent Alexander-Arnold, Danny Rose, Dele Alli and Harry Kane will probably start on the bench following their runouts in Madrid.
Even without the Liverpool and Tottenham contingents, Southgate will be confident that his team will have enough quality to maintain their prolific recent form.
England have scored 18 goals in their last five fixtures, with only four of those coming courtesy of players that ply their trade for Spurs or Jurgen Klopp's European champions.
While van Dijk´s absence should make them even more likely to find the net, they may struggle at the other end of the pitch to contain an Oranje side that hasn't failed to score in 11 matches.
Indeed, odds of 4/5 (1.80) are well worth backing on both teams getting on target for the Netherlands' eighth game in 11 in an exciting Nations League semi-final.
All odds correct at time of publish. Please gamble responsibly.