Milan stick with a three-man defence, losing Fikayo Tomori, with Rafael Leao and Olivier Giroud upfront, while Tottenham start Ivan Perisic, Dejan Kulusevski and Harry Kane.
The first leg of the Champions League Round of 16 kicks off at San Siro at 20.00 GMT.
You can follow all the build-up and action as it happens on the LIVEBLOG.
The decider will be in London on March 8 and remember the away goals rule has been scrapped in Europe.
Both sides are on poor form and with numerous absentees, as the Rossoneri are without Mike Maignan, Ismael Bennacer, Sergino Dest, Zlatan Ibrahimovic and Alessandro Florenzi, while Yacine Adli and Aster Vranckx are ineligible.
Stefano Pioli has been using a three-man defence for the last few games and finally beat Torino 1-0 on Friday, ending a run of five defeats and two draws in all competition.
Malick Thiaw impressed in that game and is again used in the back three, while Tomori was expected to return from a hip injury, but has failed a fitness test and is not even on the bench.
Rade Krunic makes up the midfield with Sandro Tonali, while Brahim Diaz completes the trident with Giroud and Leao.
It’s a more attack-minded wing-back situation with Theo Hernandez and Alexis Saelemaekers rather than Davide Calabria.
Antonio Conte has a lot of issues too, fresh from a 4-1 Premier League defeat to Leicester City, while Hugo Lloris, Rodrigo Bentancur, Ryan Sessegnon and Yves Bissouma are injured, plus Pierre-Emile Hojbjerg suspended.
The only real midfield options are therefore 22-year-old Oliver Skipp and 20-year-old Pape Matar Sarr.
There are familiar faces for Serie A, like ex-Juventus winger Dejan Kulusevski, former Atalanta defender Cristian Romero and Scudetto-winning Inter man Ivan Perisic.
The star men are Harry Kane and Heung-min Son.
Milan: Tatarusanu; Kalulu, Thiaw, Kjaer; Saelemaekers, Tonali, Krunic, Theo Hernandez; Brahim Diaz, Giroud, Leao
Milan bench: Mirante, Nava, Calabria, Ballo-Toure, Rebic, Origi, Messias, Pobega, Gabbia, De Ketelaere
Tottenham: Forster; Romero, Dier, Lenglet; Emerson Royal, Skipp, Sarr, Perisic; Kulusevski, Kane, Son
Tottenham bench: Austin, Whiteman, Sanchez, Richarlison, Danjuma, Pedro Porro, Tanganga, Moura, B Davies, Devine
Ref: Schärer (SUI)