The Italian outfit only need a point to confirm their place in the last 16 of the competition, while Genk are already certain to finish bottom of Group E.
All is not well at Napoli, whose recent troubles on the pitch have spawned a bitter fallout between the players and outspoken club president Aurelio De Laurentiis.
Carlo Ancelotti's side are currently enduring their longest Serie A winless streak since March 2010 having failed to pick up a victory since October 19, a seven-game drought which has seen them slip down to seventh in the table, already 17 points off leaders Inter Milan.
The problems have not been limited to domestic duties either, with their wait for a victory of any kind stretching back nine games across all competitions.
Seven of those nine games have ended as draws, which is all Napoli need on Tuesday, but Ancelotti will surely be viewing this match as an ideal chance to end a run of form which has placed his job under serious scrutiny.
There were reports that a failure to beat Udinese on Saturday would be the final straw for De Laurentiis and, while he did not pull the trigger following that 1-1 draw, anything other than a win against Group E's whipping boys would surely spell the end of the Italian's tenure.
Ancelotti is a man who knows how to win in the Champions League, though; he is one of only three people to lift the trophy three times as a manager and one of only seven to have won it as both a manager and a player.
Victory on Tuesday could be enough for them to finish top of the standings too, should Liverpool fail to beat Red Bull Salzburg, which would likely hand them a kinder draw in the last 16.
Despite their recent form, Napoli are a team that many of Europe's elite will be wary of coming up against; they are the only team to beat Liverpool in any competition this season and only fell narrowly short of toppling the European champions at Anfield too, so they can certainly trouble the very best on their day.
The Partenopei are unbeaten in this season's competition so far, and that record looks unlikely to end against a Genk side still searching for their first ever victory in the Champions League proper.
Indeed, the Belgian outfit have played more Champions League group games without a win than any other club (17), including five more so far this season which have yielded only one point.
The fact that the solitary point came against Napoli in the reverse fixture should give them a glimmer of hope for this match, and they will also been boosted by their first win under new boss Hannes Wolf on Saturday.
A 2-1 triumph at Cercle Brugge ended an eight-match winless run across all competitions and was only their third victory in their last 15 outings, while it was the first time in nine games that they had conceded fewer than two goals.
Genk have still not kept a clean sheet since October 26, though, and their defensive record in this competition leaves a lot to be desired with only Red Star Belgrade having conceded more than their 16 throughout the group stages.
The Belgian title holders have a particularly poor record away from home in the Champions League too, losing their last six such matches including qualifying and conceding 20 in the last four alone - an average of five per game.
Indeed, a 2007 qualifying triumph over Sarajevo is their only Champions League away win of any kind from 13 attempts, conceding 41 goals in that time while scoring only 10 - although they have found the back of the net in 33 of their last 35 European outings home and away.
Things have not gone well on the domestic front either this term, with the champions sitting eighth in the table, 17 points off the leaders, 14 points worse off than the same stage of last season and having already lost two more games this term than they did throughout the whole of 2018-19.
Napoli Champions League form: WDWDD
Napoli form (all competitions): DDDDLD
Genk Champions League form: LDLLL
Genk form (all competitions): LDLLLW
Tuesday's match will be a particularly special one for Kalidou Koulibaly, who joined Napoli from Genk in 2014 following a two-year spell with the Belgian club during which time he made 64 league appearances.
The hosts will be without Kevin Malcuit, Faouzi Ghoulam and Allan for this match due to injury, while Arkadiusz Milik is also expected to miss out again as he continues to struggle with a stomach problem.
Nikola Maksimovic had been expected to come back into the side after sitting out at the weekend, but he is now a major doubt having pulled up in training on Sunday.
Napoli possible starting lineup:
Meret; Di Lorenzo, Manolas, Koulibaly, Rui; Callejon, Ruiz, Zielinski, Insigne; Mertens, Lozano
Genk possible starting lineup:
Vandevoordt; Maehle, Dewaest, Lucumi, Neto; Ito, Cuesta, Berge, Ndongala; Samatta, Onuachu
We say: Napoli 2-0 Genk
Napoli cannot seem to buy a win at the moment, but it is hard to see anything other than a home victory in this match. Genk have a dreadful record in the Champions League, particularly away from home, and look like ideal opposition for Napoli as they bid to end a nine-game winless run.