Inter's recent results had already been mixed, but the hammer-blow of a 2-0 midweek loss to Real Madrid, which seriously jeopardises their further involvement in Europe this term, will be hard to recover from in such short order.
Sassuolo are one of three teams still unbeaten in Serie A this season, alongside leaders AC Milan and defending champions Juventus, and only once in their history have the Neroverdi recorded a longer streak without defeat in the top flight - a run of 11 games in 2015.
A relatively opportunistic win against Verona last week, when they did not create a great deal but still found the target twice, sees Roberto De Zerbi's side on 18 points from their first eight games. They then sat out any Coppa Italia and European action in midweek, with several more days to prepare for Saturday's clash than preoccupied Inter.
Undoubtedly, Sassuolo's ever-consistent Azzurri striker Domenico Berardi will be a priority for the opposition defence to keep tightly shackled. Even more so this weekend, as the club's supremely loyal all-time top scorer has scored in six of his last nine league matches against Inter. Among players currently active in Serie A, only former Nerazzurri striker Zlatan Ibrahimovic, with eight, has more.
De Zerbi has demonstrated great belief in Berardi since he took over, which has been repaid many times over with often outstanding performances for an ascendant side. Italy coach Roberto Mancini, too, has fostered the versatile forward's mid-career development, first capping the one-time Juventus player in 2018 and providing him with regular international game time.
Now Berardi is the only Serie A player to have registered more than 10 goals and assists in the calendar year, with only three other players in the top five European leagues managing to achieve this impressive feat so far in 2020 - Thomas Muller, Bruno Fernandes and Lionel Messi.
Witnessing the opposition's once-proud 'goals against' record coming apart at the seams - and with strike partner Francesco Caputo potentially back from injury - Berardi might expect to improve his stats still further at Inter's expense.
On top of their recent defensive travails, Antonio Conte's men do not often enjoy their trips to this part of Emilia Romagna, having lost seven league matches against Saturday's hosts - against no other team have they suffered more defeats in the past five years. Though - in mitigation - after a streak of four consecutive Serie A defeats against Sassuolo, the Nerazzuri have not lost any of their three most recent matches against an unlikely nemesis.
Inter travel well in general too, having won 15 of their 23 away league matches under Antonio Conte so far - losing only two - which is more than any other team since the start of last season.
However, consecutive defeats against the Spanish champions in recent weeks - at home and away - have seriously deflated Conte's assertion that they could contend on all fronts with this season's bulked-up squad.
Indeed, the come-from-behind 4-2 win against Torino last weekend was the Nerazzurri's only success in their six last games across all competitions. Romelu Lukaku was in an irrepressible mood against the Granata, saving the day with two goals and two assists, and appears entirely unaffected by the malaise which seemingly surrounds some of his teammates.
As a result, Inter are currently fifth in the table and still well within reach of Saturday's opponents as well as potential Scudetto contestants Juventus, Roma and city rivals AC Milan. A maximum return of three points from this testing assignment could be just the tonic needed to rejuvenate their flagging start to the season.
Whatever the outcome, armchair viewers would be ill-advised to switch off early during this encounter as more than a quarter of the total goals in the last half hour of all Serie A matches this season (25 out of 96) have been scored by Sassuolo (with 14) and Inter (11) combined.
Sassuolo Serie A form: WWDWDW
Inter Milan Serie A form: DLWDDW
Inter Milan form (all competitions): DDLDWL
Inter trio Daniele Padelli, midfield orchestrator Marcelo Brozovic and defender Aleksandar Kolarov are all observing quarantine and will not play a part this weekend. Additionally, Stefano Sensi and Matias Vecino are still injured and have also been ruled out.
Coach Antonio Conte must decide how and when to deploy each of his three strikers, as Alexis Sanchez scored the first goal of their comeback against Torino when handed a rare start last week, though the familiar Lautaro Martinez-Romelu Lukaku pairing is most likely.
Filip Djuricic returned from self-isolation last week and appeared a little rusty, but had been excellent for Sassuolo earlier in the season and should start again. Forward Francesco Caputo's participation is still in question due to his thigh injury, but a spot on the bench is perhaps possible for Domenico Berardi's chief foil.
The hosts also have to do without Lukas Haraslin, Filippo Romagna and Gregoire Defrel, but Jeremie Boga returned with his first goal of the season against Verona - after being out with COVID-19 - and could be poised to resume where he left off last term, when he racked up an impressive 11 goals and two assists from the wing.
Sassuolo possible starting lineup:
Consigli; Toljan, Chiriches, Ferrari, Rogerio; Locatelli, Lopez; Berardi, Djuricic, Boga; Raspadori
Inter Milan possible starting lineup:
Handanovic; Skriniar, D'Ambrosio, Bastoni; Hakimi, Barella, Gagliardini, Vidal, Young; Lukaku, Martinez
We say: Sassuolo 2-2 Inter Milan
Both clubs are rich in attacking talent and are unafraid of taking the initiative in important games such as this.
Though Sassuolo seemingly have more to defend - with their excellent start seeing them up near the top of the table - the pressure on Inter to win on Saturday is far greater. Goals from familiar sources such as Berardi and Lukaku are almost a given in what is sure to be a close-run encounter at the Mapei Stadium.