Both sides are pushing for a place in the UEFA Europa League next season, with Inter occupying fifth spot in Serie A with just two games remaining.
Lazio, meanwhile, are in with a chance of claiming the expected additional qualifying position after Napoli and Fiorentina - placed third and fourth in the table - contested the Coppa Italia final.
Inter failed to challenge for the title in Walter Mazzarri's first season in charge, but have consistently been in the top five throughout the campaign.
Edy Reja's Lazio have spent the majority of their season in mid-table, but they missed a chance to move up to joint sixth and close the gap on Inter to two points when they needed a stoppage-time goal from Stefano Mauri to draw 3-3 with Verona.
However, the Rome club remain just four points adrift of Mazzarri's men - meaning a win at San Siro would give them a real chance of snatching fifth place.
Recent history is on Lazio's side too, as they have won the last four meetings between the teams.
Inter go into the fixture looking to shake off the disappointment of losing to city rivals Milan last weekend, and forward Rodrigo Palacio has called on them to get back to winning ways and all but seal their Europa League berth.
"First and foremost it's important to beat Lazio so that we get into Europe, there are a host of clubs close behind us, so we have to win," he told Inter's official website.
"It's fundamental (we qualify for Europe). That's the objective we set ourselves. There are two tough games left to play now and we need to play well in them to achieve our objective."
Lazio travel to Milan in good form having lost just one of their last six Serie A matches, and will have fond memories of the corresponding fixture last season, which they won 3-1 almost exactly a year ago.
Reja will be without midfielder Senad Lulic after his dismissal against Verona, while Helder Postiga (knee), Emiliano Alfaro (knee) and Ederson (hamstring) are also missing.
Striker Miroslav Klose did return in Monday's draw from the bench, though, and he could start.
Inter midfielder Esteban Cambiasso serves a one-match suspension after his booking against Milan, while Juan Jesus (knee) and McDonald Mariga (muscle) are Mazzarri's only injury concerns ahead of a game that will mark club legend Javier Zanetti's final San Siro appearance.
