The Nerazzurri find themselves three points off a qualification place in Group F - widely billed as this year's 'group of death' - and need a win to realistically keep their chances of qualifying alive.
Inter have struggled in Europe this term, managing just four points from their four Champions League group games so far.
Domestically, however, the Nerazzurri have been superb, winning all but two of their first 13 games to find themselves just one point off Serie A leaders Juventus.
That fine form continued as they won their fourth league game in succession last time out - and extended their unbeaten domestic run to six games - when they beat Torino 3-0 away from home in their last game.
However, this has not translated into strong performances in the Champions League, with just one win from four games leaving them on the brink of dropping into the Europa League.
Antonio Conte's side will be desperate for a win to boost their chances, but Slavia Prague - despite lying at the bottom of the group - have been no pushovers, drawing with Inter in their first game in the competition this term and holding Barcelona away from home in their last.
Slavia Prague's domestic record this season is very impressive - they are unbeaten in 17 league games, winning 14, and have conceded just three times in this period.
Despite their defensive excellence, they remain the league's highest scorers with 36 strikes, three clear of local rivals Sparta Prague.
Two points from two fixtures against Barcelona and one against Inter is a very respectable haul, and the minnows will be looking to make life as difficult as possible for their Italian opponents on Wednesday.
Inter Milan form: DWWLWW
Slavia Prague form: WLWDWD
Conte is missing a number of key players, particularly in midfield, while he has been robbed of attacking depth as well.
In the centre of the park, Roberto Gagliardini and Stefano Sensi have been joined by Nicolo Barella on the treatment table, with the latter picking up a knee injury in the 3-0 win over Torino last time out, leaving the Italian coach light of options in midfield.
First-choice left wing-back Kwadwo Asamoah is also sidelined, meaning on-loan defender Cristiano Biraghi will continue to play in his stead on that flank and may get his first 90 minutes of Champions League football for the Nerazzurri this season.
For Slavia Prague, David Hovorka is a long-term absentee with a serious knee injury.
Slavia Prague possible starting lineup:
Kolar; Coufal, Kudela, Frydrych, Boril; Soucek; Sevcik, Traore, Stanciu, Olayinka; Masopust
Inter Milan possible starting lineup:
Handanovic; Godin, De Vrij, Skriniar; Candreva, Vecino, Brozovic, Valero, Biraghi; Lukaku, Martinez
We say: Slavia Prague 0-1 Inter Milan
Given Slavia Prague's impressive defensive record, they certainly won't make life easy for Conte's Inter and could well hold them to another draw. However, that result would be disastrous for the Nerazzurri's Champions League hopes and that desperation may just be enough to get the Serie A outfit over the line for a narrow win.