Tim Sherwood's men lost to Norwich last time out and will be hoping to avoid another domestic defeat after European progress, with the visiting Bluebirds side desperate for points.
In the nine league matches that have immediately followed a Europa League tie this season, Spurs have taken just 10 points - losing on five occasions - including the 5-0 reverse at home to Liverpool in December that eventually cost Andre Villas-Boas his job.
Tim Sherwood took the reins thereafter and his side has lost just twice in 11 league matches since then.
Thursday night saw Spurs come from two goals down in the tie against Dnipro to eventually prevail 3-2 on aggregate and progress to the last 16 of the competition, but Sherwood and his players hold loftier ambitions for next season.
A win against Cardiff is crucial if Tottenham is to maintain hope of a top-four finish and qualification for next season's Champions League.
Spurs are currently fifth - six points adrift of Liverpool - while Cardiff, in the bottom three, desperately needs to find form to avoid an instant return to the Championship.
Under Ole Gunnar Solskjaer, Cardiff has picked up just four points from seven Premier League outings and the Norwegian is under pressure to drag the Welsh side back to safety.
Jermain Defoe has this week left Tottenham to formally join Toronto, while Danny Rose (knee) Etienne Capoue (ankle) and Kyle Walker (thigh) remain doubts.
Gary Medel and Jordon Mutch are thought to be in contention for Cardiff after recovering from knocks, with Craig Bellamy available again after serving a three-match suspension.