The Spurs manager has used the cup competitions to hand opportunities to the likes of Wilson Odobert, Mikey Moore and Will Lankshear in attack, but all three will be absent when the Giallorossi travel to North London.
Odobert remains out with a hamstring injury; a nasty virus will leave Moore out of contention, and Lankshear is serving a one-match suspension following his red card in the 3-2 loss to Galatasaray earlier this month.
Brennan Johnson and Son Heung-min both started in Istanbul, and may be forced to do so again, with Richarlison also sidelined until the new year.
Dominic Solanke scored off the bench against Gala, and would ideally be allowed a rest in midweek, and the return of Timo Werner could give Postecoglou that option, but Son may also be the one given the night off.
While Spurs' backup options in attack are absent, it is their first-choice players who are missing at the back heading into this one, following the news that Guglielmo Vicario will be out for the foreseeable future after undergoing surgery on a broken ankle.
That means Fraser Forster should start in Europe again, but will also be required to face Fulham at the weekend, behind Radu Dragusin and Ben Davies, who have replaced Micky van de Ven and Cristian Romero.
Romero is in contention to return from a toe injury at the weekend, but remains doubtful, while Van de Ven is not expected to be available until mid-December at the earliest.
Rodrigo Bentancur should start as this is a rare opportunity for him to get some game time while he serves a seven-game domestic ban, and the two midfield positions either side of him are up for grabs.
Lucas Bergvall should also get another run out in the team, while any one of Yves Bissouma, Pape Matar Sarr, Dejan Kulusevski and James Maddison could also feature.
Tottenham Hotspur possible starting lineup:
Forster; Spence, Dragusin, Davies, Gray; Sarr, Bentancur, Bergvall; Johnson, Solanke, Werner