The two clubs have only ever faced each other twice before, in the 2017-18 campaign, with Cagliari winning both matches by a 2-1 scoreline.
Cagliari's slide down the Serie A table continued as they were swept aside by Napoli, who cruised to a 4-1 victory last weekend.
Gli Isolani were just four points off the top six at the end of November, but a winless run of seven matches has seen them drop to 15th in the table, just three points above the relegation zone.
Eusebio Di Francesco remains keen on playing a stylish brand of football, but his side's performances and results have declined in recent weeks, leaving them in a precarious position.
One cause of their decline has been their defensive frailties, with the Sardinia outfit conceding 14 goals in their last seven league games, taking their season's tally to 31 – only Crotone, who sit bottom of the table, have conceded more.
Di Francesco needs to find a way to shore up his backline if they are to have any chance of turning their fortunes around and moving away from danger.
A much-needed victory on Wednesday would be Cagliari's third at home this campaign and could move them as high as 11th, one point behind their opponents.
Even though La Stregoni had 25 shots and 61% possession, they were unable to break down a resilient Milan side, who also had Sandro Tonali dismissed after just 33 minutes.
Benevento, who are competing in the top-flight for only the second time in their history, have surprised many since their promotion from Serie B last season and now see survival as a real possibility.
Inzaghi's men currently sit 10th in the table, having won five of their 15 league matches, including 2-0 victories against Genoa and Udinese at the end of last month.
Securing the three points in midweek would see them remain just inside the top half, and could move them 10 points clear of the relegation zone.
Cagliari Serie A form: DLDDLL
Benevento Serie A form: DLDWWL
Cagliari left-back Charalampos Lykogiannis was shown a red card in the defeat to Napoli and so is suspended for Wednesday's match. Either Andrea Carboni or Alessandro Tripaldelli is likely to come into the starting lineup as a result.
Midfielder Marko Rog, who recently ruptured his anterior cruciate ligament, has been ruled out for the rest of the season.
Radja Nainggolan re-signed for the club on loan from Inter Milan last week and is likely to be in contention to feature in the starting lineup.
Winger Iago Falque, who has missed the last three matches, is also unavailable with a calf problem.
Filippo Inzaghi is set to stick with the 4-3-2-1 system which has brought his side so much success this campaign.
Cagliari possible starting lineup:
Cragno; Zappa, Walukiewicz, Ceppitelli, Carboni; Marin, Nandez; Pereiro, Pedro, Sottil; Simeone
Benevento possible starting lineup:
Montipo; Letizia, Tula, Glik, Barba; Schiattarella, Ionita, Improta; Insigne, Caprari; Lapadula
We say: Cagliari 1-2 Benevento
With spirits high, Benevento will fancy their chances against an out of form Cagliari side, and could come away with a narrow victory on Wednesday.