Having beaten Barcelona in the Champions League, the Nerazzurri now aim to recover from a sluggish start in Serie A, which sees them only level on points with their hosts.
Match preview
Ninth in the Serie A standings after losing four of their eight league games so far - representing the club's worst start to a season for 11 years - Inter surely welcomed one of Europe's top sides to San Siro more in trepidation than hope of winning.
However, Hakan Calhanoglu's precision strike in first-half stoppage time proved enough to earn a second Group C victory of their campaign in midweek, and the Nerazzurri's resilient performance has helped them into second spot behind Bayern Munich.
Before the crucial return fixture at Camp Nou next week, Inter must focus on steadying the ship domestically, having lost three of their last four league matches - to arch-rivals Milan, then surprise package Udinese and, finally, against Roma last weekend.
As a result, Simone Inzaghi's tenure as coach appears to be under distinct threat, and the former Lazio boss will be aware that one eye-catching result in the Champions League will count for little should his side continue to fall off the pace in Serie A.
Already eight points behind leading pair Napoli and Atalanta, Inter's first loss to Roma since 2017 leaves them stranded adrift of their main Scudetto rivals, and that 2-1 home reverse was the third occasion already where they have taken the lead but later succumbed to defeat.
Attempting to turn such form around promptly may prove a challenge, as Sassuolo have often posed a threat in matches between two unevenly-matched clubs. Indeed, Inter lost their most recent encounter, back in February: a 2-0 win for the visitors at San Siro.
In all, Sassuolo have actually won eight of their 18 meetings with Inter since promotion to Serie A - losing the same number of times - so hold a commendable record against one of Calcio's big beasts.
They also host Inzaghi's current crop at the Mapei Stadium in the rare position of sitting above the Nerazzurri in the table, as Alessio Dionisi's side are ahead by virtue of goal difference before the teams' Saturday afternoon clash.
A large part of their success so far has been vastly improved defensive displays this term, as following a 5-0 slaying of Salernitana, they have recorded five clean sheets to date - that tally is two more than in the entirety of last season and represents one of Europe's best records.
Only Barcelona have managed more shut-outs than Sassuolo across the top five European leagues, and the manner of victory against their last opponents suggests they are also finding away to replace the front four that thrived throughout 2021-22 before being dismantled in the summer.
In the absence of injured talisman Domenico Berardi, too, Dionisi's new-look attack are starting to share the goalscoring burden, but facing Inter and Atalanta in their next two fixtures will prove a sterner test of their credentials.
Sassuolo Serie A form:
D
D
D
L
W
W
Inter Milan Serie A form:
L
W
L
W
L
L
Inter Milan form (all competitions):
L
W
W
L
L
W
Team News
While Inter will again be without midfield maestro Marcelo Brozovic this weekend, Romelu Lukaku is reaching the end of his recovery and could be in contention to feature at some stage; Joaquin Correa will be sidelined, though, after picking up a hamstring injury on Tuesday.
After a hard-fought Champions League contest, Simone Inzaghi may make some changes in personnel for his team's trip to Emilia-Romagna - particularly with the upcoming visit to Barcelona in mind.
Therefore, Kristjan Asllani could start in midfield and Denzel Dumfries at wing-back, while captain Samir Handanovic replaces Andre Onana in goal.
Domenico Berardi has been absent from the Sassuolo squad since they faced Milan shortly before the international break, and he has since been recovering from a muscular injury. The Italy international is now expected to return and may be brought on from the bench.
Hamed Traore, Murt Muldur and Gregoire Defrel are all out until after the World Cup, but midfielder Pedro Obiang returned to action last week, after more than a year on the sidelines since discovering a heart condition.
In light of the hosts' strong performance against Salernitana, the same starting XI could be retained, which would see Andrea Pinamonti leading the front three versus his parent club. While on loan at Empoli last term, Pinamonti scored against Inter in May.
Sassuolo possible starting lineup:
Consigli; Toljan, Erlic, Ferrari, Rogerio; Frattesi, Lopez, Thorstvedt; Lauriente, Pinamonti, Kyriakopoulos
Inter Milan possible starting lineup:
Handanovic; Skriniar, De Vrij, Bastoni; Dumfries, Barella, Asllani, Calhanoglu, Dimarco; Martinez, Dzeko