Though Napoli are two points clear of both La Real and Dutch side AZ Alkmaar - and Gennaro Gattuso's team will definitely qualify if they avoid defeat - they could yet be eliminated if they lose. Real must match or better AZ's result in Rijeka in to secure their own progress.
Napoli stayed top of the table following their 1-1 draw in Alkmaar last week, while this Thursday's visitors from the Basque country had to come from behind twice to earn a 2-2 home draw with bottom side Rijeka, who have already been eliminated.
Even with 10 points on the board, Napoli are not safe though. A close-run three horse race has conspired to fill their final group game with jeopardy.
Both sides come into this potentially-decisive clash knowing that AZ could deny either of them a place in the last 32 if the Dutch side - who sensationally sacked coach Arne Slot in midweek - can win in Croatia.
At the end of October, Napoli stole away with a 1-0 win from San Sebastian in the teams' first ever encounter, thanks to Matteo Politano's deflected long-range strike. In that game, Gattuso's men had just a third of possession and Politano's was their only shot on target.
They were on a run of six successive Europa League group victories at home until AZ turned them over at the venue then named Stadio San Paolo on the opening night, so will fancy their chances of picking up the point required to ensure participation in the knockout stages.
Sunday's trip to Serie A bottom club Crotone ultimately resulted in a routine 4-0 win after the home side were reduced to 10 men just after half time, leaving the Partenopei third-placed in a highly competitive Scudetto race.
Having started the season like an express train, Real Sociedad come into Thursday's crunch clash on the back of a momentum-stalling run of four straight draws at home and abroad. Against local rivals Alaves on Sunday night, despite dominating the ball they failed to capitalise on their hosts' being a man short for the final half-hour.
Away from Anoeta, they have won four, drawn one and lost three of their last eight European games on the road. Not only that, but they have kept clean sheets in four of their last five away games in the group stage, winning three, which includes this season - at both Rijeka and AZ.
So with good reason, La Real boss Imanol Alguacil is confident that his charges can reverse their home defeat to Napoli this time out, stating: "We can go face-to-face with any side and we are going to Italy to win."
Last week it emerged that Imanol's enterprising side could finally stage their rescheduled Copa del Rey final against Basque rivals Athletic - which may even be the first Spanish game that permits fans to attend - on a provisional date of April 4, 2021 at Estadio La Cartuja in Seville.
In order to continue their continental campaign into next year too, they must first find a way to get through a sticky situation in Naples.
Napoli Europa League form: LWWWD
Napoli form (all competitions): WLWWDW
Real Sociedad Europa League form: WLWDD
Real Sociedad form (all competitions): WWDDDD
Gennaro Gattuso has rotated his forwards in the ongoing absence - through a shoulder injury - of summer signing Victor Osimhen. The Nigeria striker has been undergoing physiotherapy and trained alone at the start of the week, but is not ready to start.
Dries Mertens - who scored Napoli's goal in Alkmaar on his 100th appearance in UEFA club competition - is set to take his place after the more conventional 'number nine' option Andrea Petagna was preferred for Sunday's trip to Crotone.
Expected to miss out beforehand, midfielder Fabian Ruiz was deemed fit enough for a place on the bench but did not feature at the weekend, though may get some game time against his compatriots.
Key creator David Silva, Spain forward Mikel Oyarzabal and midfielder Jon Guridi have been out injured for Real recently, though Silva and Oyarzabal will be given every opportunity to make the squad by coach Imanol.
Aritz Elustondo has returned to training but is unlikely to be ready for the trip to Naples, as the Real squad rotates again in accordance with their coach's apparent philosophy.
Napoli possible starting lineup:
Ospina; Rui, Koulibaly, Maksimovic, Di Lorenzo; Ruiz, Bakayoko; Insigne, Zielinski, Politano; Mertens
Real Sociedad possible starting lineup:
Remiro; Zaldua, Zubeldia, Le Normand, Monreal; Guevara, Merino; Zubimendi, Portu, Januzaj; Jose
We say: Napoli 1-1 Real Sociedad
Napoli were out-thought and outplayed the first time these two grand old clubs met in October, so will be wary of La Real's guile and prowess.
A draw, however, is enough for the Azzurri to secure knockout football in the new year and Gattuso's side are battle-hardened enough to see this group stage campaign over the line, while Real may ultimately need the help of Rijeka to join them.