Fernando Santos's side may have picked up their second piece of silverware in the space of three years over the summer, but they are winless in Group B and need to turn things around if they are to qualify for the defence of their European Championship crown via those means.
June's Nations League triumph may not have surpassed Euro 2016 as the greatest moment in Portugal's football history, but their 1-0 victory over the Netherlands in the final is nevertheless another trophy in a cabinet which, before 2016, was conspicuously empty.
Santos's side can justifiably consider themselves among the leading nations in world football right now, then, which has made their start to qualifying all the more disappointing.
The reigning European Championship holders have drawn both games so far, and both at home too having been held to a goalless stalemate by Ukraine and then a 1-1 draw in the reverse meeting with Serbia in March.
Portugal therefore find themselves fourth of five teams in Group B - behind Ukraine, Luxembourg and Serbia - and even maximum points from their upcoming double-header against Serbia and Lithuania would not be enough for them to catch the leaders at this stage.
Cristiano Ronaldo and co do have a couple of games in hand, though, and they also boast an unbeaten record since their World Cup last-16 exit last summer - a run of 10 games which includes five wins and five draws.
Ronaldo remains the star name for Portugal, but Serbia have a few of their own and will certainly fancy their chances of picking up a second successive victory after their draw in Lisbon six months ago.
Serbia bounced back with a 4-1 triumph over Lithuania last time out and, should they follow that up with victory on Saturday and against Luxembourg on Tuesday, then their hopes of reaching the Euros for the first time as an independent country will look a lot brighter.
Portugal are the much bigger test on paper, so Serbia will be happy this match comes at home, where the Eagles are unbeaten in a competitive match since their opponents' last visit in October 2015.
Serbia form: WWDDLW
Portugal form: DDDDWW
As is always the case when Portugal play, Ronaldo will take star billing as he looks to add to his 158 caps and 88 goals at international level.
In the history of international football only Iran's Ali Daei has scored more than the Juventus icon, and despite his advancing years you would not bet against him going on to score the 22 more he needs to top the list.
Portugal already have one eye on the future as well, though, with the highly-rated Joao Felix expected to start alongside Ronaldo following his mega-money summer move to Atletico Madrid.
Ferro has impressed for Benfica this term and could be thrown straight in considering Pepe's absence through injury, although 35-year-old Jose Fonte offers a more experienced option alongside Ruben Dias.
Tumbakovic has a decision to make over vice-captain Nemanja Matic, who is yet to start a match for Manchester United this season but remains one of Serbia's most high-profile players.
Serbia possible starting lineup:
Dmitrovic; Rukavina, Milenkovic, Spajic, Kolarov; Tadic, Milinkovic-Savic, Matic, Kostic; Jovic, Mitrovic
Portugal possible starting lineup:
Patricio; Cancelo, Fonte, Dias, Guerreiro; Fernandes, Neves, Moutinho; Bernardo, Ronaldo, Felix
We say: Serbia 1-1 Portugal
Serbia will make things very difficult for Portugal, as they did in the reverse fixture in March. Portugal, of course, have the Ronaldo factor which makes them capable of winning any game - not to mention the likes of Felix and Bernardo Silva - but Serbia have the talents to nullify those threats too.
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