The Emilian clubs clash at Stadio Renato Dall'Ara, separated only by goal difference in the Serie A standings, where they both sit comfortably in mid-table.
Match preview
A second-half comeback last weekend brought Bologna three points against Torino at Dall'Ara, and notched up their fourth straight win in all competitions, so they travelled to Milan in some confidence on Wednesday.
Following a run which had put them into the next round of the Coppa Italia and lifted them clear of Serie A's drop zone, a Rossoblu side led by one of Inter's 2010 treble-winning squad, Thiago Motta, even took the lead against their illustrious opponents at San Siro, as Charalampos Lykogiannis struck in the 22nd minute.
However, it all fell apart soon after, and having gone in at the interval behind by two goals, Bologna ultimately succumbed to a morale-sapping 6-1 defeat.
Due to a better result for Sassuolo at home to Roma, Motta's men subsequently slipped down to 13th place in the table, though they remain nine points clear of the bottom three with just 90 minutes remaining before the World Cup break.
Clearly, their coach still has plenty to do in order to ensure a safe conclusion to the season, and Bologna have now lost more points from winning positions than any other Serie A side - a remarkable 17 to date. Therefore, even if they take the lead in their final fixture of the calendar year, victory will be far from a done deal.
By contrast with Saturday's hosts, Sassuolo had suffered successive defeats ahead of their own midweek engagement, at home to Jose Mourinho's Roma.
Reverses to both Napoli and Empoli had seen Alessio Dionisi's side stall, and a continuing struggle for attacking fluency saw them fail to find the net in both matches.
Yet, the Neroverdi managed to extend their unbeaten streak against their counterparts from the capital by snatching a 1-1 draw on Wednesday night, as Tammy Abraham's 80th-minute opener was cancelled out by a goal five minutes later, from struggling striker Andrea Pinamonti.
Salvaging a point took Sassuolo's home tally to 11 for the season, from seven games, but they have won just once on the road so far. Not only that, but local rivals Bologna have also been beaten on just one occasion at Dall'Ara this term.
For that reason, successfully signing off a year in which Dionisi has established himself as a worthy successor to Roberto De Zerbi - having had to deal with the decimation of his forward line in the summer - may not be straightforward.
Bologna Serie A form:
D
L
W
W
W
L
Bologna form (all competitions):
L
W
W
W
W
L
Sassuolo Serie A form:
L
L
W
L
L
D
Team News
Following their implosion at San Siro, Bologna may make some changes to the XI that started in midweek, with the inclusion of young forward Emanuel Vignato a possibility, while Michel Aebischer may return in midfield.
Almost certainly, top scorer Marko Arnautovic will start up front, after making a comeback from injury at the weekend and featuring against his former club on Wednesday. Having recently established himself as a starter, Scottish midfielder Lewis Ferguson will hope to keep his place in support of the hosts' lone frontman.
Thiago Motta should only have injured centre-back Kevin Bonifazi sidelined again, so has an almost full complement from which to choose.
His counterpart Alessio Dionisi, though, does not have the same situation, as Mert Muldur and Gregoire Defrel remain out of action; chief creator Domenico Berardi has only an outside shot of making the bench.
Maxime Lopez must serve a suspension due to accumulated bookings, so Kristian Thorstvedt is set to return in central midfield after being rested against Roma.
With Berardi still short of fitness, either Emil Konradsen Ceide or teenage winger Luca D'Andrea should start on the right flank, in support of midweek goalscorer Andrea Pinamonti.
Bologna possible starting lineup:
Skorupski; Posch, Soumaoro, Sosa, Lykogiannis; Medel, Dominguez; Aebischer, Ferguson, Vignato; Arnautovic
Sassuolo possible starting lineup:
Consigli; Toljan, Erlic, Ferrari, Rogerio; Frattesi, Harroui, Thorstvedt; D'Andrea, Pinamonti, Lauriente