Following a 2-0 win in Germany, the Scudetto favourites start the second leg of their last-16 tie in the driving seat, but their visitors can draw upon last year's Europa League heroics for inspiration.
Match preview
Napoli's two-goal victory in Frankfurt was not only their first ever victory over Eintracht, following two previous losses, but also leaves them on the verge of reaching the Champions League's last eight for the very first time.
Strikes either side of the break, from star striker Victor Osimhen and captain Giovanni Di Lorenzo, secured the Partneopei a significant advantage against opposition reduced to 10 men when Randal Kolo Muani was sent off in the 58th minute.
Having now racked up 22 goals in the competition this season, Napoli return to home soil, where they are unbeaten in their last 11 Champions League home games, winning all three so far this term and scoring at least three goals each time.
Luciano Spalletti's side may have since suffered a first league defeat at Stadio Maradona of the 2022-23 campaign, but they eased past Atalanta at their Campanian headquarters on Saturday, after wing wizard Khvicha Kvaratskhelia broke the deadlock with a dazzling solo goal.
The Georgian's strike helped his side hold an 18-point lead atop the Serie A standings, and it is surely just a matter of time before they are crowned champions for the first time in more than three decades.
With domestic glory apparently in hand, Napoli's gaze is now set on breaking new ground in Europe, and having blitzed their way through the group stage before winning their first knockout fixture, Spalletti may fancy his team can not only finish the job on Wednesday but also go all the way to Istanbul.
When their star man was shown a straight red card for lunging in late on Napoli's Andre-Frank Zambo Anguissa, defeat seemed inevitable for a Frankfurt side already trailing to fiendishly difficult opponents in last month's reverse fixture.
The Italian club's visit to Deutsche Bank Park did not go to plan in any aspect from the hosts' point of view, as Eintracht recorded both their fewest shots (five) and most shots against (18) in any of their seven Champions League games this season.
Left with a steep uphill task to claw their way back into the tie, Die Adler's form since does not suggest they can cause such an upset, as a run of one loss and two draws in the Bundesliga has seen them slip to sixth in the standings.
Now five points shy of the all-important top four, Frankfurt were held to a 1-1 home draw by lowly Stuttgart on Saturday, when Sebastian Rode scored with their only shot on target.
Having lifted the Europa League trophy last term, though, Oliver Glasner's men have still lost just three of their last 20 matches in Europe while recording 10 wins in the process, so will not travel to Naples without hope.
They have also won by a three-goal margin or more on five separate occasions this season and have already scored more Bundesliga goals (46) than throughout the whole 2021-22 campaign. Furthermore, they have found the net in all three of their Champions League away games this year, winning two out of three in the group stage.
History also offers a positive omen for those that believe, as Eintracht's only previous visit to Napoli ended in a 1-0 UEFA Cup win back in December 1994 - also at the last 16 stage. However, they have to score at least twice this time around.
Napoli Champions League form:
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Napoli form (all competitions):
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Eintracht Frankfurt Champions League form:
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Eintracht Frankfurt form (all competitions):
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Team News
After serving a two-match domestic suspension for being sent off against former club Empoli, left-back Mario Rui will be at Luciano Spalletti's disposal again on Wednesday and should replace Mathias Olivera in Napoli's back four.
The hosts also hope to see first-choice goalkeeper Alex Meret return after he withdrew following the warm-up ahead of last week's win over Atalanta.
Kim Min-jae is set to overcome a knock too, while Hirving Lozano could shake off his muscular injury in time to take a place on the bench; Giacomo Raspadori is still sidelined by a thigh problem.
Capocannoniere leader Victor Osimhen leads the line up front, ably supported by Khvicha Kvaratskhelia, who has provided four assists in the Champions League this season - the most ever for Napoli during a single campaign. He has also generated the most scoring opportunities after a ball carry of any player in the competition (16), firing in 12 shots and creating four chances.
Frankfurt, meanwhile, will be without suspended striker Randal Kolo Muani in Naples, with Eric Junior Dina Ebimbe and Danish forward Jesper Lindstrom both unavailable due to injury.
Oliver Glasner can still call upon Daichi Kamada to feature in an attacking trio led by Rafael Santos Borre, and the Japan international is the club's all-time top scorer in UEFA competition, with 14 goals in 36 appearances.
Borre may have found the net just three times in all competitions this term but scored several crucial goals on the road to Europa League glory last year.
Napoli possible starting lineup:
Meret; Di Lorenzo, Kim, Rrahmani, Rui; Anguissa, Lobotka, Zielinski; Politano, Osimhen, Kvaratskhelia
Eintracht Frankfurt possible starting lineup:
Trapp; Tuta, Hasebe, Ndicka; Buta, Sow, Rode, Max; Kamada, Gotze; Borre