Spurs won the reverse fixture 5-0 in London last month thanks to doubles from Son Heung-min and Harry Kane, as well as an effort from Erik Lamela, but they may find life a little tougher in the Serbian capital.
Red Star are unbeaten in 12 across all competitions at home and have just one defeat in their last 12 in Belgrade in the Champions League.
That loss came at the hands of Paris Saint-Germain, while last season they managed to beat eventual champions Liverpool 2-0 at the Stadion Rajko Mitic and also held Italian outfit Napoli to a 0-0 draw.
Tottenham go into the game in second spot in Group B with four points, one clear of Red Star in third.
Spurs boss Mauricio Pochettino will be able to call on striker and stand-in skipper Harry Kane after he missed the draw at Everton last time out with a virus.
Defender Jan Vertonghen sits out due to a hamstring injury and Lamela is absent with a thigh problem, while captain Hugo Lloris is a long-term absentee and so Paulo Gazzaniga will continue in goal.
It had been suggested Son may be left out after his involvement in the serious injury sustained by Everton’s Andre Gomes at Goodison Park at the weekend.
The South Korean was visibly distraught when the extent of the injury became apparent on the pitch. He has since been receiving support and Pochettino says the 27-year-old is now in a “good way” and available for the trip to Serbia.
Red Star remain without long-term injury victim Branko Jovicic, while fellow midfielder Aleksa Vukanovic is a doubt after missing the 2-0 win at Proleter over the weekend with an ankle injury.