While irrepressible Inter recently claimed the Scudetto, their hosts are deep in trouble at the other end of the standings, with a 10-year stay in the top flight at risk of reaching its end.
Match preview
After being crowned Italian champions with five games remaining, Inter continued their title celebrations by beating 10-man Torino last week; keeping them on course to surpass 100 points by the end of a remarkable season.
With 89 on the board so far, they will now try to break the 90-point barrier for just the third time in club history - a final total of 97 in 2007 is the Milanese giants' all-time best.
Simone Inzaghi's side had already wrapped up their 20th Scudetto in grand style, beating city rivals AC Milan in the Derby della Madonnina, and their latest league victory of a dominant campaign was owed to Hakan Calhanoglu's second-half brace - the latter strike came from the spot, and the Turkish midfielder has now scored all 16 penalties he has taken in Serie A.
Calhanoglu joins prolific forward pairing Lautaro Martinez and Marcus Thuram in double figures for the season, with the trio helping Inter build a 29-game unbeaten streak in the top flight - their last league loss was at home to Sassuolo, last September.
Such has been the Nerazzurri's all-round supremacy, not only have they seemed to score goals at will but they can also set a new club record for most clean sheets in a single season by shutting out their hosts on Saturday.
One more would take them past a mark first set 35 years ago, and their current total of 20 is also the best throughout Europe's top five leagues this term.
Inter's only Serie A defeat this season came against Sassuolo, when the Emilian side stunned San Siro with a 2-1 victory sealed by Domenico Berardi's winner and seemed to be on course for another mid-table campaign.
However, having been thumped 5-1 by Fiorentina last week - soon after losing 3-0 to relegation rivals Lecce - the Neroverdi are deeply mired inside the bottom three and star man Berardi has been sidelined by injury for some time now.
Davide Ballardini's side sit 19th in the standings, five points adrift of safety with just four games to play, and have won only one of their last 15 league matches.
Sassuolo have kept a single clean sheet during that time, and 10 years after making their Serie A debut, the prospect of relegation looms large in Reggio Emilia.
With Genoa, Cagliari and in-form Lazio still to play, points may be hard to come by between now and the end of the season, and taking anything from Saturday's contest will be considered a major bonus.
Sassuolo Serie A form:
L
D
D
D
L
L
Inter Milan Serie A form:
D
W
W
D
W
W
Team News
As Federico Dimarco and goalkeeper Yann Sommer featured in full training earlier this week, both should be available at the Mapei Stadium; however, Francesco Acerbi is set to miss out again due to injury.
Simone Inzaghi is not expected to rotate his squad despite already securing the title, but Dimarco could displace Carlos Augusto on the left flank and Denzel Dumfries returns from suspension to vie with Matteo Darmian for selection on the right.
Ex-Sassuolo star Davide Frattesi will also hope to force his way into the visitors' engine room, alongside Hakan Calhanoglu, who has scored more goals for Inter in a single league season (13) than any midfielder since Lothar Matthaus netted 16 in 1990-91.
Up front, Capocannoniere favourite Lautaro Martinez - who made his debut against Sassuolo in August 2018 - will aim to end a goalless streak stretching back to February in the Italian top flight.
Though only Martinez (seven) has scored the opening goal more times than Andrea Pinamonti (six) in Serie A this season, the latter has scored just once in nine league matches against former club Inter since leaving Milan.
Pinamonti will be reunited with Armand Lauriente this weekend, after the French forward served a suspension against Fiorentina, but centre-back Ruan Tressoldi is now ruled out by a one-match ban.
Gregoire Defrel (calf), Marcus Pedersen (back), Samu Castillejo (knee) and long-term absentee Domenico Berardi (Achilles) are all sidelined by injury.
Sassuolo possible starting lineup:
Consigli; Toljan, Erlic, Ferrari, Doig; Racic, Boloca; Volpato, Thorstvedt, Lauriente; Pinamonti
Inter Milan possible starting lineup:
Sommer; Pavard, De Vrij, Bastoni; Darmian, Barella, Calhanoglu, Frattesi, Augusto; Thuram, Martinez