Harry Redknapp's team will be without Ledley King, Jermain Defoe and Michael Dawson but it's the loss of the suspended Rafael van der Vaart which will be the most keenly felt.
Since swapping the Bernabeu for White Hart Lane, the Dutchman has rocketed up the Castrol Rankings, jumping from 503rd to 83rd in September alone! Playing regular football has made a significant difference and he was inspired against Twente in Spurs' last Champions League game.
In barely an hour on the pitch he had five shots on target, which is the best ratio in the competition so far this season. He grabbed the first goal in the 4-1 win but was later sent off for a second bookable offence, putting him out of the trip to San Siro.
Without their flying Dutchman, Spurs' next most threatening player looks to be Gareth Bale. The gifted Welshman first registered on the Castrol Rankings at number 1809 last December, but a series of excellent displays have seen him rise to number 78 from number 444 last May.
Recently linked with a move to Real Madrid, Bale was in great form against Twente providing an assist for Roman Pavlyuchenko and scoring the final goal in the 4-1 win, which earned him 7.79 out of 10 for his performance. In the Premier League he's done even better, getting rankings of 8.88 and 9.47 for his displays against Wolves and Stoke City.
Spurs will be without their highest ranked player Jermain Defoe (18), who is out through injury, so will need to rely on Peter Crouch (502) for goals. Inter old boy Robbie Keane is unlikely to see any action and his omission from the team has seen him tumble down the rankings to number 1427, having been at 391 in January.
Despite boasting the current Champions League holders, Italy's Serie A only has one player in the Top 20 of the Castrol Rankings. Just to slap Inter in the face even more, that accolade belongs to Milan's Alexandre Pato, who checks in at number 19.
Incredibly, the highest ranked Inter player is goalkeeper Julio Cesar at number 60. The Brazilian shot-stopper has kept four clean sheets in the past five matches.
Inter's inspiration is likely to be Samuel Eto'o, who is in devastating form for the Nerazzurri. Often seen playing as a winger in the Jose Mourinho era, the three times Champions League winner has been unleashed by Rafael Benitez, climbing the Castrol Rankings from 172 to 85 in the last month alone.
In the Champions League Eto'o has been devastating, scoring the equaliser against Twente in the 2-2 draw and netting a hat-trick against Werder Bremen last time out. He also provided the assist for Wesley Sneijder's goal in the 4-0 rout. Eto'o earned a ranking of 9.49 for his virtuoso display against the Bundesliga team.
Inter's six Champions League goals have been scored by just two players - Samuel Eto'o and Wesley Sneijder. Like his compatriot Van der Vaart, Sneijder was released by Real Madrid and has excelled since moving to Serie A.
Sneijder is currently at number 78 in the Castrol Rankings, which is just shy of his best ranking of 69 last January. The Dutchman scored against Twente and added another in the Bremen demolition during which he provided an assist for Eto'o.
For all the striking talent on both teams, they have goalkeepers who both feature in the top two of their most effective players in the Castrol Rankings. Tottenham's Heurelho Gomes is ranked 34th. with his fellow Brazilian Julio Cesar being Inter's most effective performer at number 60 overall in the rankings.
It all points towards an intriguing contest between the holders and the Champions League rookies at San Siro.