Neither team can qualify for next summer's World Cup in Brazil, but the home side's Real Madrid star, the most expensive player in the world, is set for a cameo off the bench
Wales' slim hopes of reaching Brazil 2014 finished with a 2-1 loss to Macedonia in Skopje, while Serbia were held 1-1 by second-placed Croatia in Belgrade.
Those results leave Wales second-bottom of Group A while Serbia sit in third place, some nine points adrift of Croatia with just two games remaining.
Gareth Bale is 11/2 with BetVictor to open the scoring against Serbia
Wales' goalscorer on that occasion, Gareth Bale, completed his £86 million transfer from Tottenham to Real Madrid last week but was not fit to play for his country in Macedonia due to a foot injury.
And while the 24-year-old will not start the match against Serbia at the Cardiff City Stadium, Wales manager Chris Coleman has revealed his star man may be able to make a substitute appearance.
"He's never going to be ready to start, it's as simple as that," he told BBC Sport.
"The fact he's turned up and is trying to be fit for us is such a huge positive and if he's ready then he may play a part.
"We'll see how he reacts between now and Tuesday."
Sinisa Mihajlovic's side, meanwhile, will be hoping for a win to secure third place in the group and a favourable seeding for the 2016 European Championships qualifying campaign.
However, they will not be able to call on midfielder Nemanja Matic as he is suspended after being sent off against Croatia.