Neck-and-neck in the Group F standings with five points to their name, the Magpies currently have the edge over the Rossoneri on goal difference, but both sides still need results elsewhere to go their way if they are to dine at Europe's top table that little bit longer.
Match preview
The great VAR debate was reopened when Newcastle pitted their wits against French champions Paris Saint-Germain two weeks ago, where an Alexander Isak strike in the first half had the Magpies on the verge of arguably their most famous continental triumph in history.
However, as the ball bounced off of Tino Livramento's thigh and onto his elbow in injury time, referee Szymon Marciniak saw fit to award PSG a last-gasp penalty, which Kylian Mbappe converted to deny the Magpies all three points in the cruellest and most controversial of circumstances.
It is not all doom and gloom for the third-placed hosts just yet, though, as Newcastle still possess the superior head-to-head tally against PSG - who are only two points better off - so victory on Wednesday coupled with Les Parisiens' failure to beat an already-qualified Borussia Dortmund would send Eddie Howe's team through.
Any other scenario would either force the Magpies down to Europa League football or send them packing from the continent entirely, and despite soldiering on admirably through their wealth of injuries, a lack of options appears to have caught up to Howe's team at the worst possible time.
Indeed, Newcastle's most recent two Premier League clashes with Everton and Tottenham Hotspur have seen the Magpies suffer consecutive losses by an aggregate score of 7-1, but neither of those contests took place at St James' Park, where eight of Newcastle's last nine in all competitions have seen the hosts prevail.
Working around an unenviable injury list has been nothing new for Milan head coach Stefano Pioli either, but the road to the last 16 is a little more complicated for the Rossoneri, whose penultimate Group F clash at home to Borussia Dortmund was a chastening affair.
The German outfit sealed their place in the knockout rounds via a 3-1 success on the San Siro soil, three weeks after the Rossoneri had kept their dwindling hopes alive by beating PSG on home turf, and they begin the final matchday sat bottom of the 'group of death' rankings.
Newcastle will go through with a win and a PSG draw, but Milan's head-to-head goal tally is inferior to the French champions, so Pioli's side must triumph at St James' Park and hope that Dortmund defeat PSG if they are to sneak into the second last-16 spot.
As was the case with Newcastle, Milan also came out on the wrong end of a five-goal thriller away from home in Saturday's Serie A clash with Atalanta BC, coming from behind twice only to succumb to a Luis Muriel strike in the fifth minute of second-half injury time, which made it four games without an away win for Pioli's team.
The Rossoneri have conceded 10 goals on rival turf over that stretch, but they were stunted in a 0-0 draw during their maiden meeting with Newcastle at San Siro in September, where the Magpies faced a 25-shot onslaught and still left with a point. However, as only a victory will do for both teams on Tyneside, goalless lightning should not strike twice on Wednesday.
Newcastle United Champions League form:
D
W
L
L
D
Newcastle United form (all competitions):
L
W
D
W
L
L
AC Milan Champions League form:
D
D
L
W
L
AC Milan form (all competitions):
W
D
W
L
W
L
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Team News
While Newcastle's dampening loss to Tottenham was best consigned to the back of Howe's mind, the Magpies boss received a major double injury boost, as both Callum Wilson and Sean Longstaff were able to make appearances off the bench following their respective layoffs.
An abundance of injured players are still absent alongside banned ex-Rossoneri midfielder Sandro Tonali, though, including Nick Pope (shoulder), Jacob Murphy (shoulder), Dan Burn (back), Elliot Anderson (back), Harvey Barnes (foot), Sven Botman (knee), Joe Willock (calf), Matt Targett (thigh) and Javi Manquillo (groin).
Wilson's comeback is unlikely to threaten Isak's spot at the tip of the attack, but Longstaff is now in line to return to the engine room over 17-year-old Lewis Miley, who has capitalised on his teammates' fitness woes to shine for the Magpies over the past few weeks.
As mentioned, the Milan medical team have also been kept busy with a number of injury victims themselves, including defenders Malick Thiaw (hamstring) and Pierre Kalulu (tendon), both of whom are expected to remain out until 2024.
The absences of Marco Pellegrino (heel) and Simon Kjaer (muscle) have left Fikayo Tomori as Milan's only fit central defender, so Theo Hernandez should provide emergency cover once again, as Alessandro Florenzi takes the Frenchman's place at left-back.
Striker Noah Okafor (thigh) and goalkeeper Marco Sportiello (calf) complete the stricken list for the Rossoneri, but in a major boost, much-coveted winger Rafael Leao - who has been nursing a thigh concern of his own - is expected to be passed fit for the trip to England and should therefore demote Christian Pulisic to the bench.
Newcastle United possible starting lineup:
Dubravka; Trippier, Lascelles, Schar, Livramento; Joelinton, Guimaraes, Longstaff; Almiron, Isak, Gordon
AC Milan possible starting lineup:
Maignan; Calabria, Tomori, Hernandez, Florenzi; Loftus-Cheek, Reijnders, Musah; Chukwueze, Giroud, Leao
We say: Newcastle United 3-2 AC Milan
When the going gets tough at St James' Park, Newcastle are almost always able to deliver, and facing a Milan side with only one fit central defender is exactly what the doctor ordered for a decimated Magpies squad.