This Thursday, they travel to Alkmaar for a crucial meeting with Dutch side AZ, who could complete a famous double over the Partenopei with a home win.
Napoli now have their destiny within their own hands and can clinch qualification for the knockout phase with a victory in the Netherlands after beating bottom side Rijeka 2-0 on a night when AZ and Real Sociedad drew 0-0 in Alkmaar.
That set of events gave a fresh twist to a fascinating three-way battle for two qualifying spots that has been underway more or less from the opening night.
Gennaro Gattuso's men began with a home loss against their Dutch counterparts, but are now two points clear of Arne Slot's side with two games left to play.
The clubs' first European encounter produced a significant surprise as AZ defeated their Neapolitan hosts by virtue of a 57th-minute Dani de Wit strike, thus ending the Serie A side's six-match group stage winning run.
As a result, Napoli have now won just one of their seven matches against Dutch opposition and have yet to claim a victory in the Netherlands - a statistical quirk which they will be keen to iron out in the process of sealing progress this week.
Sunday's Serie A clash with rivals Roma was already set to be a momentous occasion in the calendar, but a richly deserved 4-0 win at San Paolo - soon to be renamed after the club's favourite son - was imbued with new meaning after the untimely death of Diego Maradona.
Dries Mertens scored the third goal on the night, on which emotional tributes to the all-time great were paid. The Belgian star, who has proved an enormous success since signing from PSV several years ago, registered five goals in his eight Eredivisie games against Thursday's opponents AZ - including a hat-trick on his farewell appearance for Utrecht back in May 2011.
It should come as no surprise that AZ are still in contention alongside two such successful clubs from Europe's major leagues as they have finished in the top two of their Europa League section on four occasions, most recently last season when they tallied 15 goals in finishing runners-up to Manchester United.
Slot's side were denied the chance to go for glory in the Eredivisie last term, after Ajax were awarded the title when league action was prematurely culled last spring. Many astute observers had them as favourites to topple the Amsterdam giants in a closely-run race.
The Alkmaar club extended their unbeaten European home run to 11 matches last week but could not take their opportunities and had to settle for a 0-0 draw against La Liga leaders Real Sociedad.
Substitutes Myron Boadu and Zakaria Aboukhlal almost combined for the winner in the last minute but Aboukhlal could only head over from close range. It was a frustrating end to a fine performance that leaves a side whose league position has been suppressed by too many draws in need of a win on Thursday.
On Sunday, AZ completed a 2-1 win at Heracles, with Boadu - recently returned from illness - at the heart of the performance throughout. That win left them seventh in the standings but already 10 points adrift of leaders Ajax, as a result of their propensity to take one point from games rather than all three.
In other circumstances, a point on Thursday night would be a more than satisfactory outcome against such a Serie A heavyweight, but coach Slot will know that another famous win could be needed to stay in contention.
AZ Europa League form: WWLD
AZ form (all competitions): WLWWDW
Napoli Europa League form: LWWW
Napoli form (all competitions): LWWLWW
Forward Myron Boadu has begun to strike form after returning from a spell on the sidelines so should be awarded with another start, either in a front three or as part of a pair.
Napoli's big-money buy Victor Osimhen is unavailable due to a shoulder injury, so either Dries Mertens or Andrea Petagna will deputise up front.
Amir Rrahmani is unavailable due to continuing self-isolation, though full-back Elseid Hysaj has reportedly tested negative for COVID-19 and is set to return to Italy. The Albanian international served a quarantine period in his homeland, but will not return to the camp in time for Thursday's game.
AZ possible starting lineup:
Verhulst; Wijndal, Martins Indi, Chatzidiakos, Svensson; Stengs, Koopmeiners, Midtsjo; Gudmundsson, De Wit, Boadu
Napoli possible starting lineup:
Ospina; Ghoulam, Maksimovic, Koulibaly, Di Lorenzo; Demme, Bakayoko; Elmas, Zielinski, Politano; Petagna
We say: AZ 1-1 Napoli
This closely-fought group could go down to the wire, with improving AZ now starting to turn draws into wins domestically and more than holding their own in Europe so far.
Napoli's momentous week - capped with a stunning four-goal win against a serious Scudetto rival - may have sapped both legs and minds, so a close-run draw between two entertaining sides is the probable outcome.