Two wins and two defeats from their four group stage games this time around means it would be the ideal time for the France forward to end that drought and point a clear path to the knockout stages.
Having come so close last time around, failure to get out of the group might be the final nail in Neymar's dream of bringing Champions League glory to the French capital.
However, the man who carries the greatest weight when it comes to the fortunes of Thomas Tuchel's side might just reside at the other end of the field.
Marquinhos stepping into Silva's shoes
Having taken the armband from his fellow Brazil international, the 26-year-old centre-back has shown he can be just as influential – most recently in last week's 1-0 win over RB Leipzig.
"Playing higher was also the plan against Leipzig but it was not possible," Tuchel said when pondering the potential tactical approach against United.
"If the game requires playing low, we have to provide answers on the pitch. That is why it was necessary to find defensive solutions against Leipzig."
Marquinhos was the man who came up with the answers more often than not, making three interceptions, seven recoveries and conceding a solitary foul over the course of the 90 minutes.
What happens to PSG when their skipper is not around this season is perhaps even more instructive.
He sat out the opening two games of the Ligue 1 season with coronavirus, with Tuchel's threadbare squad suffering back-to-back 1-0 losses versus Lens and Marseille.
Marquinhos' return sparked a run of eight consecutive victories domestically. He missed the 4-0 win over Nimes due to an adductor complaint, which also ruled him out of the 2-1 home reverse against United.
Either side of his heroics against Leipzig, Marquinhos looked on as PSG lost 3-2 at Monaco before being held to a 2-2 draw by Bordeaux last weekend.
Dominating from central areas
As well as being PSG's premier centre-back, over the past 18 months, Marquinhos has also made a strong case for being their best holding midfielder, presenting Tuchel with plenty to ponder before a game where stopping United's counter-attacking threat is likely to be vital.
"I'm not going to answer you now," he told reporters when asked which position Marquinhos would take up.
"This is also a question that [Ole Gunnar] Solskjaer is very interested in, so I can't tell you."
Irrespective of which position is his most effective, something that can alter depending on the opponent, it is hard to escape the conclusion PSG have no way of adequately replacing Marquinhos' qualities when he is not around.
Mbappe and Neymar are unquestionably generational talents. But the likes of Angel Di Maria, Mauro Icardi and Julian Draxler have all produced match-winning brilliance during their time at the Parc des Princes.
In defence, Tuchel has the lavishly gifted Presnel Kimpembe, but the sense is that everything is far more likely to fall apart without Marquinhos' guiding hand.
Since the start of last season in the Champions League, his 28 tackles, 21 interceptions and 93 recoveries are the best of any PSG player, with only Kimpembe (41) and Silva (39) bettering his 38 clearances.
Over the same period, PSG have won 21 out of 26 matches in Ligue 1 with Marquinhos in the side, losing three. That win percentage of 80.8 falls to 69.2 in the 13 matches he has missed.
PSG also have three defeats in those games, set against nine wins and a draw. Their goals against per game climb slightly from 0.8 to 0.9 despite the smaller sample size.
This latest lap of the Neymar saga is likely to be enthralling, as Mbappe seeks to get his turbo-charged engine running once more. But perhaps another man holds the keys when it comes to PSG's ambitions of standing on the top step of the Champions League podium.