This time around in the teams' seventh meeting since 2011, Massimiliano Allegri's men are in poor form, having won only three of their first eight games in Serie A. The script for the past few years has been similar, with a plethora of Rossoneri players out with injury, with fans doubting the innovative brilliance of Milan's supposed state-of-the-art MilanLab.
Against Barcelona, Allegri will line up in his usual 4-3-3 formation, where it's predicted that Riccardo Montolivo will play as a No. 10 to give Milan a more defensive mindset in the center of the park.
Between the pipes, Christian Abbiati's injury will mean that the inconsistent Marco Amelia will start from the first minute. Interestingly enough, one of Amelia's best games came a few years ago against Real Madrid in the Champions League.
The defense will see Philippe Mexes back in the lineup while he's currently serving a four-game suspension in Serie A for punching Giorgio Chiellini. He'll have his usual partner Christian Zapata alongside him, with the speedy Ignazio Abate on the right and converted winger Kevin Constant on the opposite flank.
Despite Abate's flaws, his searing speed is a welcome attribute against a team like Barcelona that field a lightning-quick attack consisting of Alexis Sanchez, Neymar and the immortal Lionel Messi.
Needless to say, there's quite a mismatch right there.
The midfield three will have the most rigorous job in the world, having to contain the famed tiki-taka and negate Barcelona's suffocating high pressing.
Nigel de Jong will be Milan's defensive midfielder and could even shift to the back like he has previously when Allegri's men need more steel. Alongside the former Manchester City man, expect to see the box-to-box midfielder Sulley Muntari, who is Milan's top scorer in Serie A with three goals, and the versatile Andrea Poli.
Here's where it gets interesting. Even though Allegri told La Gazzetta dello Sport that there are promising signs in Mario Balotelli's recovery, he's still listed as questionable for the match against Barcelona with a muscular injury to his thigh.
If he doesn't start, expect to see Robinho playing a free role around Alessandro Matri, who has been woeful so far since joining from Juventus in the summer. He's still looking for his first goal with Milan and has been whistled mercilessly by the San Siro faithful.
There's also a chance that the surprising Valter Birsa will get the nod from the beginning. If this is the case, then Montolivo will move back to the midfield and Andrea Poli will most likely sit on the bench.
Either way, it'll take a gargantuan effort from Allegri's men if they want a repeat of that stunning 2-0 home win against Barcelona last season.