Richarlison had been missing since the 4-0 win over Everton in mid-August, with an issue that was often shrouded in mystery by manager Ange Postecoglou.
The Brazilian returned to the matchday squad at the weekend though, and was brought on for the final 10 minutes as Tottenham cruised to a 4-1 win over West Ham United.
Also back from injury at the weekend was Son Heung-min, with the Spurs skipper finding the net in an eight-minute spell where Postecoglou's side finished West Ham off early in the second half.
After missing South Korea duty though, and only just being passed fit to face West Ham at the eleventh hour, Son could be given a rest here to protect him for the weekend trip to Crystal Palace.
Returning from suspension is Radu Dragusin, as the central defender sat out the win over Ferencvaros after being sent off inside 10 minutes against Qarabag on matchday one.
That will provide Postecoglou with the opportunity to rest both Cristian Romero and Micky van de Ven, and after playing twice for Romania during the international break, Dragusin's match fitness is assured.
On the injury front, two players that could have been of great use to Postecoglou will miss out, as a hamstring injury to Wilson Odobert and groin strain picked up by Djed Spence will rule them both out.
Having now played 90 minutes in six successive matches, Pedro Porro could be in line for a rest, but that would require Archie Gray to move into an unorthodox full-back role again, but the teenager was widely praised for his performance at centre-back against Ferencvaros.
Another young prodigy, Mikey Moore, also received rave reviews for his performance in Budapest, and the 17-year-old could be rewarded with another start in attack here for Tottenham.
After scoring in both Europa League games so far, and in seven straight matches for club and country, Brennan Johnson's hot streak finally came to an end at the weekend, and the Welshman is likely to start as a substitute here.
James Maddison was pulled off at half time in the win over West Ham at the weekend, posing a possible injury concern, but it was soon confirmed that the decision was purely tactical, and the midfielder is available, even though it is likely he will also be rested.
Tottenham Hotspur possible starting lineup:
Vicario; Gray, Dragusin, Davies, Udogie; Sarr, Bentancur, Bergvall; Moore, Richarlison, Werner