On one of the most important nights in the cultural calendar, the defending champions visit San Siro desperately in need of a win to haul back their Milanese counterparts, who still top the Serie A standings.
After another win on Sunday, league leaders Milan remain top of the pile - just ahead of relentless city rivals Inter Milan - with an impressive 37 points already accrued. In midweek, their prestigious visitors arrive in the unfamiliar position of fifth, some ten points behind - but with a game in hand.
Unfortunately though, both sides have been struck by a series of injuries and illnesses this week, which could well have a major bearing on the outcome on Wednesday night.
It was a strong-willed performance by the injury-hit Rossoneri to take all three points against overachievers Benevento at the weekend, as midfielder Sandro Tonali was sent off in the first half, with Milan already a goal to the good through Franck Kessie's penalty.
A 2-0 win, sealed by Rafael Leao - still deputising for the injured Zlatan Ibrahimovic - proved not only the mental mettle of Stefano Pioli's side but also their ability to absorb pressure against the odds.
They are unlikely to face 25 shots on Gianluigi Donnarumma's goal again this time out, even against far superior opposition, but are equally unlikely to take a totally gung-ho approach to their encounter with the Old Lady of Turin.
Although their scintillating attacking stats draw most attention, Milan also have the third-best defensive record in Serie A this term.
Even since the absence of 'King Zlatan', the Rossoneri have also maintained their remarkable run of scoring at least two goals in their past 35 league games, while avoiding defeat in the league since last March.
Losing that precious record against Juventus is almost unthinkable for their success-starved tifosi, who would love nothing more than holding off Inter and denying the Bianconeri a tenth successive title in May.
Now clearly ahead in the Capocannoniere charts on 14 goals, Juventus talisman Cristiano Ronaldo netted another pair of goals in Sunday's comfortable 4-1 victory over Udinese - a win which they will hope to use as a warm-up for their biggest test of the season so far.
Their over-reliance on one man to carry the attack though - as Juve have only the sixth-best goalscoring record in Serie A this season and Ronaldo has scored nearly half of them - has undermined any sustained attempt at catching up with the leaders.
Therefore, the chief reason for the Bianconeri's current double-digit points deficit to Milan is clearly apparent. Juventus have recorded six draws in Serie A this season after 14 games played, with many of those failures to seal maximum points coming in the absence of their Portuguese superstar.
In fact, the last time that Juve drew so many of their games at this point was back in 2001-02, when they did actually go on to lift the title under the guidance of club legend Marcelo Lippi.
It will take a comeback of seismic proportions to achieve a similar feat this time around though, as both Milan clubs look to go from strength to strength.
If the impossible dream is going to occur in Andrea Pirlo's first season in charge, Juventus must not only resist the Rossoneri's super-efficient attack on Wednesday, but also break a notable current run of failure against the league's bigger boys such as Roma, Lazio and Atalanta.
In short, all three points at San Siro are essential - even at this relatively early stage of the season - so underperforming stars such as Paulo Dybala and Aaron Ramsey are required to step up their game against a fresh-faced and motivated Milan outfit.
AC Milan Serie A form: WDDWWW
AC Milan form (all competitions): WDDWWW
Juventus Serie A form: WWDWLD
Juventus form (all competitions): WWDWLD
Due to extraordinary circumstances, both clubs will be without integral players for Wednesday's clash but Milan coach Stefano Pioli will be worst-hit, as Zlatan Ibrahimovic, Ismael Bennacer, Matteo Gabbia and Alexis Saelemaekers trained separately from the main squad on Monday are not yet ready to be involved.
Meanwhile, Juventus have second-top scorer Alvaro Morata (muscle injury) plus full-backs Juan Cuadrado and Alex Sandro (both COVID-19) out of action, so Danilo will start in defence and Paulo Dybala continues up front.
AC Milan possible starting lineup:
Donnarumma; Dalot, Kjaer, Romagnoli, Hernandez; Calabria, Kessie; Castillejo, Calhanoglu, Hauge; Leao
Juventus possible starting lineup:
Szczesny; Danilo, Bonucci, de Ligt, Frabotta; Rabiot, Bentancur, Ramsey, Chiesa; Dybala, Ronaldo
We say: AC Milan 1-1 Juventus
The tantalising prospect of this encounter has kept Juventus hopes alive over the break, as they chase a historical 10th league win on the spin from behind the pack.
However, bringing Milan's seemingly endless unbeaten run to a conclusion on Wednesday will prove devilishly difficult, as Pioli's much depleted side are made of sterner stuff.