The Islanders ended a 17-game wait for a league win at the weekend and are now within two points of safety, while Bologna are 11th after beating Lazio 2-0 last time out.
Cagliari have spent the past six weeks in the relegation zone but, just when hope seemed to be dwindling, they revived their survival hopes with a 2-0 win at Crotone.
Semplici's side now have the chance to move above the dotted line in midweek, though for that to be a possibility they need Torino to lose away at Lazio on Tuesday.
Cagliari may have finally ended their winless run last time out, but they have still gone nine games without a victory on home soil, losing six of those.
Indeed, the Islanders have failed to score in their last two home league matches and could make it three in a row for the first time since December 2012.
That is something Bologna will be aiming to take advantage of as they look to break into the top half of the table.
Sinisa Mihajlovic's side were one of four to go unbeaten in the Italian top flight in February, with Inter the only team to concede fewer goals (one) than Bologna's two.
The visitors are in good shape heading into this contest, then, and are now within two points of Sampdoria in 10th.
Victory will therefore be the target for Bologna on Wednesday as they seek a Serie A double over Cagliari for the first time since 2013-14.
Cagliari Serie A form: LWLLLW
Bologna Serie A form: LLWDDW
Cagliari had to hold on for the final 15 minutes against Crotone with 10 men after Charalampos Lykogiannis was sent off, meaning that the left-back will miss this game through suspension.
Kwadwo Asamoah was brought on for his first appearance of the campaign and is in contention to fill in for Lykogiannis on Wednesday night.
One player certain to start is Pedro, who has scored a Serie A goal once every 102 minutes on average against Bologna - five goals in 512 minutes - which is his best ratio against any side he has faced more than twice in the competition.
As for Bologna, Mihajlovic has no fresh injury concerns so he may go with the same XI that started the win against Lazio.
That would mean another start for goalkeeper Lukasz Skorupski, who has made the most saves (43) of any Serie A keeper in 2021.
Cagliari possible starting lineup:
Cragno; Ceppitelli, Godin, Rugani; Nandez, Duncan, Nainggolan, Marin, Asamoah; Pavoletti, Pedro
Bologna possible starting lineup:
Skorupski; De Silvestri, Medel, Soumaoro, Dijks; Dominguez, Svanberg; Orsolini, Soriano, Sansone; Barrow
We say: Cagliari 0-2 Bologna
Cagliari's win against Crotone has restored hope of moving out of the relegation zone and new boss Semplici will be eager to build some momentum.
However, Bologna have won two and drawn two of their last four matches and we can see them coming away from the Sardegna Arena with all three points on Wednesday.