Lautaro Martinez, Joaquin Correa and Hakan Calhanoglu lead the way for Inter, but Empoli adjust their tactics to support Francesco Caputo.
It kicks off at the Stadio Giuseppe Meazza at 19.45 GMT.
You can follow all the build-up and action as it happens on the LIVEBLOG.
The Nerazzurri are still celebrating their 3-0 mauling of rivals Milan in the Supercoppa Italiana, which was played in Riyadh last week.
That trophy will be presented to the fans before kick-off, although there is also tension around how Milan Skriniar will be welcomed by fans after rejecting a contract extension.
Marcelo Brozovic and Samir Handanovic are still out injured, while Romelu Lukaku is only fit for the bench.
Joaquin Correa gets a rare start, giving Edin Dzeko a rest, as he partners Lautaro Martinez, while Stefan de Vrij steps in for Francesco Acerbi.
Empoli are unbeaten in four, including a comeback from 2-0 down to draw 2-2 with Lazio.
Razvan Marin sits out a ban, while Lorenzo Tonelli, Mattia Destro, Alberto Grassi and Ardian Ismajli are on the treatment table.
It’s a special game for Martin Satriano, who is on loan from Inter, but he is on the bench after a change of system.
Inter: Onana; Skriniar, De Vrij, Bastoni; Darmian, Barella, Calhanoglu, Mkhitaryan, Dimarco; Correa, Lautaro Martinez
Empoli: Vicario; Ebuehi, De Winter, Luperto, Parisi; Akpa Akpro, Henderson, Bandinelli; Cambiaghi, Bajrami; Caputo