Inter have Stefan de Vrij back and start Mauro Icardi with Matias Vecino, while Empoli rely on Francesco Caputo and Diego Farias.
It kicks off at San Siro at 19.30 UK time (18.30 GMT).
This is the most important game in the final round of the season, as it is where the battles for Champions League places and Serie A safety intersect.
Inter need a victory to be sure of a top four finish, although if Atalanta beat Sassuolo then it’ll only be enough for fourth due to an inferior head-to-head record.
Empoli know a win, or at least matching Genoa’s result with Fiorentina, will ensure they avoid relegation.
Luciano Spalletti has a full squad to choose from, as De Vrij has recovered from an injury that saw him miss games against Chievo and Napoli.
Matias Vecino steps in for Roberto Gagliardini in midfield following a 4-1 defeat at the San Paolo, with Politano also shaking off a knock to accompany Radja Nainggolan and Ivan Perisic.
Icardi leads the attack, chosen instead of Lautaro Martinez or Keita Balde Diao.
Empoli have not been able to get Rade Krunic fit in time, so he is out of action along with Luca Antonelli, Antonino La Gumina, Kevin Diks and Lorenzo Polvani.
Domenico Maietta starts in defence rather than Frederic Veseli, with Marko Pajac and Giovanni Di Lorenzo as wing-backs.
Afriyie Acquah, who scored in last week’s 4-1 win over Torino, is again in midfield to replace injured Krunic.
Francesco ‘Ciccio’ Caputo kept his training regime to a minimum over the last week to ensure he did not strain his muscles and is therefore able to start alongside Diego Farias.
Inter: Handanovic; D'Ambrosio, De Vrij, Skriniar, Asamoah; Vecino, Brozovic; Politano, Nainggolan, Perisic; Icardi
Empoli: Dragowski; Maietta, Silvestre, Dell'Orco; Di Lorenzo, Acquah, Bennacer, Traoré, Pajac; Caputo, Farias