The European champions have the advantage of playing on home turf and face a Swiss side who have lost two of their last four away matches.
Vladimir Petkovic's side, however, secured qualification for the final four with an astonishing 5-2 comeback victory against Belgium and were the top scoring of all 12 sides who contested the group stages in League A.
These two nations met in qualification for the 2018 World Cup, with Portugal winning 2-0 at home and Switzerland claiming a victory by the same scoreline in front of their own fans.
Despite that close recent record, it is the hosts who are clear favourites, priced at 13/20 (1.65) with bet365 to win in 90 minutes. Petkovic's men are offered at 9/2 (5.50) with the draw available at 13/5 (3.60).
Switzerland have practically a fully-fit squad with the only player absent through injury being Schalke forward Breel Embolo. Xherdan Shaqiri will be available after being left on the bench in Liverpool's Champions League final win on Saturday.
Portugal will be lead by captain Cristiano Ronaldo, who returns to the squad after not featuring in the group stages, while Benfica youngster Joao Felix is in the squad. Joao Mario and Andre Gomes are not included, while the side's top scorer in the competition so far, Andre Silva, is injured.
Given Portugal's status as continental champions, England's run to the World Cup semi-finals last year and the general resurgence around a young and exciting Netherlands side, it seems many people have simply dismissed Switzerland's chances.
The Alpine nation had the best qualifying record of all four finalists, scoring more goals, claiming more wins and amassing more points than any of their more illustrious rivals for the title.
There should therefore be an argument for trying to get the Swiss onside and while they may not ultimately go on to win the title, they should be able to compete extremely well on Wednesday night.
Tips and predictions
Backing Switzerland/Draw in the double chance market at 23/20 (2.15) should be of real interest. Portugal's last four matches in all competitions have all ended as draws, and another stalemate would bring profit from this selection.
Also worthy of consideration is backing the visitors to win either half at 7/4 (2.75) while the same price is offered for a first half Swiss goal.
Odds correct at the time writing. Please gamble responsibly.