The Lilywhites staged a dramatic late comeback against PSV Eindhoven last time out and now require three more points against Inter in midweek if they are to remain on course for a top-two finish in Group B.
After kicking off a massive week in style with a 3-1 win over Chelsea, and with Arsenal to come on Sunday, Mauricio Pochettino has a number of big selection calls to make.
Here, Sports Mole looks at how Spurs could line up against the 2010 European champions.
Tottenham are likely to still be without Trippier for the visit of Inter, while fellow full-back Rose is also ruled out indefinitely, so Ben Davies and Serge Aurier will continue to operate down the flanks.
Jan Vertonghen returned to the bench against Chelsea following a two-month layoff, however, and is therefore in contention to feature on Wednesday, though Pochettino will surely not want to risk the centre-back in such a big game.
The Argentine coach made four changes between the wins over Crystal Palace and Chelsea, including the returns of Christian Eriksen and Son Heung-min in attacking midfield. After both played a major part in the victory over Chelsea, it is unlikely that either man - fitness permitting - will be left out here.
Pochettino does tend to favour Harry Winks for European matches, however, so one of Moussa Sissoko - who has thrived since being given a run in the side - or Eric Dier may well make way in the engine room.