While Inter have won five from five to storm clear at the top of the table, their visitors are far more inconsistent - but the Emilian side upset the odds by beating Juventus last time out.
Match preview
After continuing their flawless run to a fifth league match by beating Empoli at the weekend, early Serie A leaders Inter will now try to win six on the spin at the start of the season for just a third time in club history.
Only Antonio Conte (2019) and legendary European Cup-winning coach Helenio Herrera (1966) have achieved such a feat as boss of the Nerazzurri, but Simone Inzaghi can join them this week, by steering his side to success against Sassuolo.
A stunning strike from Federico Dimarco topped Inter's tally up to 15 points from a possible 15 on Sunday, when the wing-back's 51st-minute goal saw off last-placed Empoli at Stadio Castellani.
Having already beaten Monza, Cagliari, Fiorentina and arch-rivals Milan - the latter pair by four-goal margins - Inzaghi's men are peerless in Italy right now, though they could only take one point from last week's Champions League opener away to Real Sociedad.
While both failed to find the net in Tuscany, the strike partnership of summer signing Marcus Thuram and new captain Lautaro Martinez has gelled well, and Inzaghi has had to fend off suggestions that the Scudetto is already Inter's to lose.
There is, of course, a long way to go before any silverware is handed out this season, but having confirmed his reputation as a cup specialist since moving to San Siro, Inzaghi surely has half an eye on the main prize.
Therefore, Inter cannot afford to slip up at home to teams in mid-table, and having won five of their last six league matches against Sassuolo in the league, only another win will do on Wednesday.
Despite their negative recent record against Inter, over a longer period Sassuolo actually possess a creditable set of results versus the Nerazzurri in Milan.
From 10 Serie A fixtures played between the clubs at San Siro, there have been four wins for each side, although the Emilian team were beaten 4-2 there last season.
That scoreline has twice cropped up again for Alessio Dionisi's men over the past few days, as after capitulating during the second half of a 4-2 defeat to promoted Frosinone, six more goals were shared in Sassuolo's spectacular home game against Juventus at the weekend.
A handling error from Wojciech Szczesny gifted them an early lead, and long-time Juve target Domenico Berardi - who missed the start of this season while a transfer to Turin fell through - also got his name on the scoresheet, before Federico Gatti capped off a special night for Sassuolo supporters with a comical own goal.
While all of their points this term have come at home, Sassuolo have lost six of their last seven away matches in the league stretching back to last season, failing to win once.
Since the beginning of the 2022-23 campaign, the Neroverdi have also conceded more goals on the road than any other Serie A side (44 in 21 matches), so a trip to San Siro should cause some trepidation for Dionisi and co.
Inter Milan Serie A form:
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Sassuolo Serie A form:
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Team News
Facing a trip down south to Salerno at the weekend, Inter may make a handful of changes in midweek, with Nicolo Barella and Denzel Dumfries both set for a return to the starting lineup.
As Marko Arnautovic has suffered a thigh injury that could keep him out until November, Simone Inzaghi will choose between Marcus Thuram, Alexis Sanchez and Lautaro Martinez to form the front pair in his familiar 3-5-2 formation. The latter made his Inter debut against Sassuolo in 2018 and has since scored five league goals against them, only netting more against Cagliari (nine) in Serie A.
Former Sassuolo midfielder Stefano Sensi is still out of action due to a thigh problem, though Juan Cuadrado may make his return from a tendon issue in time to take a place on the bench.
The visitors, meanwhile, hope to welcome back first-choice goalkeeper Andrea Consigli following a two-game absence, but Alessio Cragno remains on standby to deputise once again; Agustin Alvarez could therefore be Sassuolo's only absentee.
After scoring against Juventus, ex-Inter striker Andrea Pinamonti already has four goals this season, just one goal shy of his final total from 32 appearances last term; however, he has scored only once in eight league meetings with his former club.
More impressively, the Neroverdi's talisman Domenico Berardi has netted seven times against Inter in Serie A - among active players, no one has more.
Inter Milan possible starting lineup:
Sommer; Pavard, De Vrij, Acerbi; Dumfries, Barella, Calhanoglu, Mkhitaryan, Dimarco; Martinez, Thuram
Sassuolo possible starting lineup:
Cragno; Toljan, Viti, Erlic, Vina; Boloca, Henrique; Berardi, Bajrami, Lauriente; Pinamonti