Hugo Lloris may be rested with the Chelsea clash in mind as Pierluigi Gollini is handed the gloves, while two changes at full-back could see Matt Doherty and Ben Davies replace Emerson Royal and Sergio Reguilon respectively.
The up-and-coming Oliver Skipp could retain his place in the middle alongside Harry Winks, while Tanguy Ndombele - who made the squad for the first time under Nuno at Selhurst Park - may be drafted in for Pierre-Emile Hojbjerg.
Spurs' attacking options have taken a hit following injuries to Son Heung-min, Ryan Sessegnon and Steven Bergwijn, meaning that spots on the wings have opened up for Jack Clarke and Bryan Gil to impress the new manager, although Bergwin could yet be passed fit after travelling with the team.
Dane Scarlett will certainly be holding out for a start up top if Harry Kane is rested as expected, but with Rennes representing Spurs' most formidable opponent in the group, Nuno may want one experienced attacker in Lucas Moura to feature from the off.
Tottenham possible starting lineup: Gollini; Doherty, Rodon, Tanganga, Davies; Skipp, Ndombele, Winks; Clarke, Lucas, Gil body check tags ::