Claudio Ranieri's visitors, meanwhile, have posted back-to-back victories of their own to stay within arm's length of their hosts.
Establishing themselves as a regular fixture in the top half of the standings over recent years, Sassuolo have built a reputation for attacking football - even against the top sides - and travelled to meet Milan on Wednesday in a confident mood.
Having succumbed to inconsistency in the second half of the season, the Neroverdi had finally put together successive Serie A wins for the first time since October last weekend, before staging a sensational second-half fightback at San Siro.
Throwing bodies forward in the final 20 minutes, Sassuolo were ultimately rewarded when youth team product Giacomo Raspadori netted from close range, before adding a well-taken second in the 83rd minute to end their hosts' title hopes once and for all.
Though they are well set for another top-half finish this season, in recent weeks the Neroverdi had started to stall. However, three straight victories - with their two previous successes coming versus struggling Benevento and then free-falling Fiorentina last Saturday - have now seen them pull closer to the top seven.
Now that Roberto De Zerbi's team have won consecutive away games in Serie A for the first time since November, they will expect to keep their good run going upon returning to their Emilian headquarters.
Still in with an outside chance of posting their best league finish since 2015's seventh spot, Sampdoria travel to the banks of the Secchia seeking to reduce their seven-point deficit to four - with a further five games left to play.
Experienced coach Claudio Ranieri will hope his side can at least stay ahead of fast-fading Verona to claim ninth, after a 1-0 win over Serie B-bound Crotone on Wednesday went a long way to assuring a top-half finish.
Evergreen veteran Fabio Quagliarella claimed the decisive goal against the Squali - his tenth strike of another productive season, including one in the reverse fixture against Sassuolo - thereby helping his side to end a rocky run on the road.
Ahead of their midweek trip to Calabria, the Blucerchiati had won only one of their last eight away games in the top flight, keeping just a single clean sheet in the process. Therefore, an in-form Sassuolo side - who have registered 15 goals in their last seven games after a relatively barren spell beforehand - will represent a real threat at the Mapei Stadium.
With Ranieri's future being a regular point of discussion in the Italian media of late, the former Leicester City boss has insisted that all focus remains on securing his team's stated target of 52 points; so, while several past Samp sides have tended to switch off once safety has been secured, the much-admired tactician has no intention of letting that happen this term.
Centre-forward Francesco Caputo is expected to remain sidelined for Sassuolo this weekend - along with long-term injury victim Filippo Romagna - but Kaan Ayhan can re-join the squad after returning a negative COVID-19 test and could take a spot on the bench.
Following his heroics in Milan, primavera product Giacomo Raspadori should start up front for the visitors as Gregoire Defrel misses out, while on-loan Maxime Lopez - who pledged his future to the club last week - is expected to come back into the XI for the suspended Filip Djuricic.
Veteran midfielder Albin Ekdal (thigh) has also sat out the last two games and could return to the squad, with Morten Thorsby and Adrien Silva set to stay ahead of the Sweden international in the pecking order.
In defence, Lorenzo Tonelli covered the suspension of Maya Yoshida against Crotone, but could now drop out of Sampdoria's back four as Yoshida returns, while - despite his match-winning contribution last time out - 38-year-old Fabio Quagliarella is due a rest and Keita Balde could step in up front.
Sassuolo possible starting lineup:
Consigli; Toljan, Chiriches, Ferrari, Rogerio; Locatelli, Lopez; Berardi, Traore, Boga; Raspadori
Sampdoria possible starting lineup:
Audero; Ferrari, Yoshida, Colley, Augello; Candreva, Thorsby, Silva, Jankto; Gabbiadini, Balde
We say: Sassuolo 2-2 Sampdoria
Despite their commitment to a front-foot approach - or perhaps because of it - Sassuolo have won just five of their 15 home fixtures this term, so they may once more dominate the ball but fail to keep the back door shut.
Samp have not exactly excelled on the road, with goals at a premium, but Claudio Ranieri has various attacking options fit and available this time out, so they can steal back to base with a point.