The Lilywhites' late recovery against PSV Eindhoven in their most recent Group B outing kept their slim hopes of progression alive, but a point for Inter will send the Italian side through at Tottenham's expense.
It is just about all still to play for in Group B thanks to Harry Kane's dramatic double against PSV three weeks ago, but even Mauricio Pochettino admits that his side's chances of progression are incredibly slim.
Beating an in-form Inter is one thing; following that up with a victory away at Barcelona - which Spurs will likely have to do to finish above the Italians - is another matter entirely.
Still, that is a scenario Tottenham supporters would happily have accepted a month ago when drawing 2-2 at PSV - a result that effectively left them needing three wins from three to finish in a top-two spot.
The draw in the Netherlands followed 2-1 and 4-2 defeats to Inter and Barcelona in their first two matches, leaving the North London outfit winless in five on the continent heading into that return match against PSV at Wembley on November 6.
If not for a couple of Kane goals in the final 12 minutes to overturn Luuk de Jong's second-minute opener, this visit of Inter would have been a dead rubber. As it is, Pochettino will field his strongest available XI in the hope of drawing level on points with Inter ahead of his side's trip to Camp Nou on the final matchday, on the same night that the Nerazzurri play host to bottom side PSV.
Tottenham's win against PSV got them back on track in more ways than one, having lost their previous two European matches at Wembley against heavyweight sides Juventus and Barcelona. Going further back, their record is a positive one - five wins from seven at the national stadium in this competition.
Pochettino's men also head into this must-win match on the back of a five-game winning run in all competitions, most recently overcoming Chelsea 3-1 at the weekend to climb above their London rivals into third place in the Premier League.
Spurs, who are also into the last eight of the EFL Cup, produced one of their best all-round displays in recent times to inflict a first defeat on Chelsea and are now one of the continent's most in-form sides. After kicking off a huge week in impressive style, the pressure remains on as Tottenham desperately attempt to keep their Champions League campaign alive.
Recent form in Champions League: LLDW
Recent form (all competitions): WWWWWW
Two months on, Inter's late turnaround against Tottenham in the clubs' opening Group B fixture looks all the more important, with Mauro Icardi and Matias Vecino pouncing in the closing stages at San Siro for a huge win.
Inter followed up that comeback victory with another two-goal turnaround, this time at the Phillips Stadion as they edged out PSV 2-1, before taking a point from their double-header against Barcelona over the past five weeks.
The Nerazzurri are therefore in a strong position heading into their final two matches, requiring just a point at Wembley to progress into the knockout stages for the ninth time in nine attempts, though defeat in the English capital and all of a sudden the pressure is on to get a result at home to PSV.
Losing matches is not something Inter tend to do at the moment, though, losing just two of their last 13 in all competitions and winning 10 of those. As well as being on the brink of a place in the last 16 of the Champions League, Luciano Spalletti's charges are also third in Serie A and just a point off Napoli in second.
A three-goal win against Frosinone at the weekend was exactly what Inter needed heading into this big match, two weeks on from a 4-1 humbling at the hands of Atalanta BC, but Spalletti must now decide whether to set out his side to sit back at Wembley or go in search of goals.
Inter, winners of this competition in 2010, are not exactly the best travellers as their 2-1 win at PSV ended a run of five successive away defeats on the continent, while also marking their first victory in nine attempts.
Finishing second to Barcelona would be a big achievement for the fallen Italian giants, though, having failed to reach this stage since the 2011-12 season. After years of underachieving, picking up the result needed at Wembley to finish above Tottenham and PSV would mark a new chapter in Inter's proud history.
Recent form in Champions League: WWLD
Recent form (all competitions): LWWDLW
Tottenham are expected to be without Kieran Trippier for the second match running due to a groin strain that also ruled him out of international duty with England, while Davinson Sanchez, Mousa Dembele and Vincent Janssen are out until next year.
Danny Rose is also expected to sit out the next few weeks, so Pochettino's hand has been forced somewhat in the full-back department, though he does at least have Jan Vertonghen back in his squad following a two-month layoff.
Moussa Sissoko has also done little wrong in the engine room and should retain his spot, though Harry Winks tends to perform well on the continent, so an identical XI to the one that started against PSV is a possibility.
In terms of the visitors, star defender Sime Vrsaljko has recovered from a biceps injury and is part of Inter's travelling party.
Icardi, who has 10 goals in 11 games overall, is also fit to start, meaning that Spalletti will likely stick with his favoured 4-2-3-1 formation.
The biggest call for Spalletti to make comes in attacking midfield, where Keita Balde and Ivan Perisic are battling for a starting spot on the left, with the latter being preferred against Frosinone last time out.
Tottenham Hotspur possible starting lineup:
Lloris; Aurier, Foyth, Alderweireld, Davies; Winks, Sissoko; Eriksen, Dele, Son; Kane
Inter Milan possible starting lineup:
Handanovic; Vrsaljko, De Vrij, Skriniar, Asamoah; Vecino, Brozovic; Politano, Nainggolan, Perisic; Icardi
Head To Head
Inter's 2-1 win against Tottenham in September was the latest in a series of fascinating battles between these two sides, having also played out a couple of entertaining games in the 2010-11 season.
Spurs lost 4-3 at San Siro in a match best remembered for Gareth Bale's hat-trick, before turning the tables with a 3-1 victory in the reverse fixture as both sides progresses through.
Goals were on offer in their 2012-13 Europa League last-16 tie, meanwhile, with Tottenham progressing on away goals after a thrilling 4-4 draw on aggregate.
We say: Tottenham Hotspur 2-1 Inter Milan
The onus is on Tottenham Hotspur as they require all three points on Wednesday evening. That could change the complexion of the match somewhat, with Pochettino's men having to get at their opponent, and if they can replicate their Chelsea performance then they should pick up the result that is required.