In a repeat of last season's quarter-final, Benfica come into this one already eliminated and Inter have sealed their place in the knockout stage, but group positions could still be very important for both.
While progression is already beyond them, Benfica will look to finish off a rotten group campaign by at least salvaging a Europa League spot, and in doing so, not being the only team to finish on zero points.
Along with Royal Antwerp, Benfica are the only other side still yet to pick up a point in the group stage so far following four defeats from four.
A 2-0 defeat at home to Red Bull Salzburg on matchday one means Benfica will likely need to better their result this week before then beating the Austrians on matchday six to take third place.
Their European form is in stark contrast to how impressive they have been domestically, where they currently top the tree thanks to a recent win over Sporting Lisbon in their fierce derby.
That dramatic late comeback saw them score two injury-time goals to take all three points, and a win in the last 32 of the Taca de Portugal over the weekend means they have still not lost domestically since the opening day of the season.
Regardless of what happens here, the structure of the group means that a win over Real Sociedad on matchday six will see Inter top the section, either by points or on head-to-head.
Bettering Real's result is perhaps more important for Inter though, as they are lagging behind on goal difference, but returning to the ground where they won 2-0 in April, Simone Inzaghi will hope to lead his team to another win over Benfica.
A 1-0 win in the reverse for Inter hugely flattered Benfica, as on another day, the Nerazzurri could easily have scored five or six.
The win has helped them to go unbeaten in their first four Champions League games for the first time since 2009-10 - the season when Jose Mourinho led them to glory.
Inter enter the match in incredible form too, as a draw away to title rivals Juventus maintained an excellent 10-game unbeaten run which has seen them win eight.
A shock defeat by Sassuolo remains Inter's only blemish after 17 matches in all competitions, as they fought back from going behind for the first time in 12 outings on Sunday night to earn a draw at the Allianz Stadium.
Manager Roger Schmidt picked a relatively strong Benfica side at the weekend despite being heavy favourites in the cup.
The hosts were also able to welcome back Orkun Kokcu after injury, with the Turkish midfielder making a 12-minute cameo.
Alessandro Bastoni is the big injury absentee for Inter after a calf injury, which saw him miss Italy's recent internationals, ruled him out for a month.
That was yet another defensive injury for Inzaghi to deal with after Benjamin Pavard's gruesome knee problem sidelined him, but there was a return for Juan Cuadrado against his former club Juve on Sunday.
The Colombian right-back made his first appearance in two months off the bench, and he could return given Inzaghi's persistence in rotating his full-backs in this competition.
Federico Dimarco has often been rested in the group stage, with Carlos Augusto coming in, and that could be one of the few amendments to the team which may look largely similar to the one which took to the field against Juventus.
Alexis Sanchez should return to the squad after missing Sunday's game due to playing twice for Chile during the international break.
Benfica possible starting lineup:
Trubin; Antonio Silva, Otamendi, Morato; Joao Neves, Florentino Luis, Joao Mario, Aursnes; Di Maria, Musa, Rafa Silva
Inter Milan possible starting lineup:
Sommer; Darmian, De Vrij, Acerbi; Cuadrado, Barella, Frattesi, Calhanoglu, Carlos Augusto; Thuram, Martinez
We say: Benfica 0-1 Inter Milan
A rotten campaign could well continue for Benfica, as they face an Inter side in imperious form.
Despite their fine domestic start, Benfica have looked miles off it on the continent, especially in the reverse where the Nerazzurri were utterly dominant despite the narrow scoreline, and any sort of repeat will yield the same outcome here.
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