Mauricio Pochettino will have to decide who to select at left back - due to usual starter Danny Rose's suspension and natural replacement Ben Davies' absence through injury.
Two alternative possibilities include central defenders Jan Vertonghen or Kevin Wimmer.
Rose and Davies join Erik Lamela and Toby Alderweireld on the 'unavailable' list as Spurs travel to in-form Chelsea, hoping to become the first team since North London rivals Arsenal in September to defeat Antonio Conte's side.
However, this fixture's history is certainly not on Spurs' side - as the Lilywhites have not tasted victory at Stamford Bridge since February 1990.
Despite the omens and the absentees, Spurs look set to recall Christian Eriksen to the starting line-up after the Denmark international was benched in favour of Harry Winks for Tottenham's disappointing Champions League loss to Monaco in midweek.
Eriksen is expected to take his place behind centre-forward Harry Kane, with Heung-min Son also playing a supporting role. The trio will need to be on top form if they are to help Spurs become the first team to score against Chelsea - after the Blues' six-game run of clean sheets, which shows little sign of ending anytime soon.
Tottenham's defensive unit is likely to see captain Hugo Lloris play behind a back four of Kyle Walker at right back, Eric Dier and Vertonghen in central defence - and the nod at left back potentially going to Wimmer.
The Austrian defender has recently played in the position for his country and would offer a viable option that would avoid further disruption to Spurs' defence by keeping Vertonghen in his usual central role.
A centrally-fielded Vertonghen may also be essential if Spurs are to limit the impact of Chelsea's Diego Costa - who has scored 10 goals in 12 league games; Costa's three assists mean that he has been involved in more goals than any other Premier League player so far this season.
Providing the much-needed support to Pochettino's patched up defence should be the combative Victor Wanyama - with the link between defence and attack being forged by the talented pair of Mousa Dembele and Dele Alli in central midfield.
Here is the predicted Tottenham Hotspur line-up in full.