The Rossoneri swept aside concerns about their domestic form to secure a famous Champions League success in midweek, while their hosts have just lost three games on the spin to slip down the table.
Match preview
Wednesday's shock 3-1 victory over Real Madrid at the Bernabeu not only boosted Milan's hopes of reaching the Champions League knockout phase but also ended the Spanish giants' 15-game home unbeaten streak in UEFA's top club competition.
Goals from Malick Thiaw, ex-Real and Atletico Madrid striker Alvaro Morata and Dutch midfield dynamo Tijjani Reijnders decided an open contest in the Italian side's favour, with a revived Rafael Leao having a hand in all three.
Having out-thought legendary ex-Milan coach Carlo Ancelotti, current boss Paulo Fonseca eased some of the pressure on his shoulders, as his team moved level on points with Real in the 36-team standings.
It was only the Rossoneri's second continental win of the season, after recording successive defeats - to Liverpool and Bayer Leverkusen - before beating Club Brugge late last month.
With Slovan Bratislava, Red Star Belgrade, Girona and Dinamo Zagreb next on the schedule, a playoff place now seems well within their grasp, and Fonseca will be keen to keep momentum building in Milan's last game before the international break.
Last week's 1-0 victory over nearby Monza took the second-city club onto 17 points, only good enough for seventh spot in the table, eight points adrift of Napoli at the Serie A summit.
Now, Milan will seek a fifth clean sheet in eight away games when they head for Sardinia, where they have scored at least once on all of their last 13 league visits.
All told, Cagliari have won only one of their last 39 top-flight meetings between the clubs - and none since May 2017 - while losing no fewer than 30 times in the process.
Indeed, the Rossoblu have been beaten in eight of the last nine, scoring just three goals, so precedent is certainly set against them this weekend.
The Sardinian side will also be bidding to avoid a fourth straight Serie A defeat, after losing 2-1 to Lazio on Monday evening, when they were on course for a point when Zito Luvumbo scored a second-half equaliser in Rome.
However, their hosts then regained the lead from a penalty, and immediately after the restart, Yerry Mina was shown a second yellow card, before Michel Adopo swiftly followed him down the tunnel due to dissent.
Cagliari are therefore one of seven teams separated by one point near the foot of the standings - and some dismal home form has not helped.
Davide Nicola's men have failed to score in four of their six matches at Unipol Domus so far; in addition to conceding at least twice in seven of their last eight league outings overall, that looks like a recipe for relegation.
Cagliari Serie A form:
W
D
W
L
L
L
AC Milan Serie A form:
W
W
L
W
L
W
AC Milan form (all competitions):
L
W
W
L
W
W
Team News
After recalling Rafael Leao and playing Yunus Musah in a more advanced role against Real Madrid, it remains to be seen whether Paulo Fonseca will retain both men on Saturday, when Samu Chukwueze could be brought back into Milan's starting lineup.
Long-term absentees Ismael Bennacer and Alessandro Florenzi are still on the sidelines through injury, but Matteo Gabbia could return from a calf problem.
Christian Pulisic is set to continue supporting Alvaro Morata in the final third, having averaged a goal every other game this season; the USA forward netted his only Serie A brace against Cagliari, during last term's 5-1 win at San Siro.
Meanwhile, Zito Luvumbo's first league goal for Cagliari came against Milan at Unipol Domus, back in September 2023. After his strike against Lazio earlier this week, the Angola international will be keen to keep his place, having been dropped towards the end of October.
As Yerry Mina and Michel Adopo will both be missing due to suspension, Jose Luis Palomino and Razvan Marin may be promoted from the bench.
Fortunately for Davide Nicola, they should be the Rossoblu's only absences, having reported a clean bill of health.
Cagliari possible starting lineup:
Scuffet; Zappa, Palomino, Luperto, Augello; Marin, Makoumbou; Zortea, Gaetano, Luvumbo; Piccoli
AC Milan possible starting lineup:
Maignan; Emerson, Tomori, Pavlovic, Hernandez; Reijnders, Fofana; Chukwueze, Pulisic, Leao; Morata
We say: Cagliari 0-2 AC Milan
Milan have scored a league-high 65% of their goals in the first half this season, while only two teams have found the net less than Cagliari before the break.