The Neapolitans will expect maximum points from their latest continental assignment, as they battle with Spain's Real Sociedad and AZ Alkmaar of the Netherlands for a place in the knockout stages.
Napoli's opening home defeat by the Dutch side was effectively cancelled out by a welcome 1-0 away win of their own in the Basque country - Matteo Politano's deflected long-range strike supplied the Serie A side with three welcome points at Estadio Anoeta.
The Partenopei's win in Sociedad offered them the opportunity to effectively seal progress in back-to-back games with modest Rijeka, and Gennaro Gattuso's side duly claimed a fifth successive Europa League away win in Croatia last time out.
Despite sitting deep with a five man defence, the hosts - who had less than a quarter of possession - were unable to prevent a rotated Napoli XI from overturning an early Robert Muric goal at the Stadion Rujevica to claim a deserved 2-1 result. Back-up striker Andrea Petagna led the line on that occasion and is likely to be a Europa League specialist for coach Gattuso, having often impressed when given the opportunity this term.
Though their eyes are primarily fixed on a serious Scudetto push in Serie A, Napoli's Europa League record is certainly a formidable one and they can expect to go deep into this season's competition.
The Azzurri have competed in the knockout phase on seven previous occasions and have never failed to qualify - progressing as group winners on the two most recent occasions and winning all six matches in 2015-16 while setting the current record for the most goals scored (22) in a Europa League group.
Despite their disappointing weekend defeat to leaders AC Milan, which leaves them sixth in Serie A, Napoli are clearly specialists at this level and are overwhelming favourites to complete the double over their Croatian visitors on Thursday night.
Rijeka coach Simon Rozman's side are perhaps just pleased to be involved at this stage, having snatched a surprise 1-0 victory at Copenhagen in the playoffs to make it into the group stage for the first time in three years. The Croatian club have participated in three previous Europa League group stage campaigns - all between 2013 and 2017 - but have yet to make further progress and once more look set to drop out before Christmas.
Having not played a competitive game since November 8 - a home win against NK Lokomotiva - the Whites are coming into this most challenging of fixtures stone cold. That result left the club from the Adriatic port city comfortably in mid-table, having played several games fewer than their rivals due to a number of postponed fixtures in this virus-disrupted season.
Surely the highlight of their European history was a group phase win against AC Milan in 2017 - their only victory ever against Italian opposition. A shock of similar proportions will be required this week if Rijeka are to retain any slim hope of knockout football in the new year.
It may well be a particularly challenging return to familiar surroundings for Rijeka's Italian defender Armando Anastasio, who is on a season-long loan to the club from Monza. The left-back was born in Naples and learned his trade in the Napoli academy, so will be all too familiar with the power and ingenuity of the Partenopei's play, as his new club confronts its toughest European test yet.
Napoli Europa League form: LWW
Napoli form (all competitions): WWLWWL
HNK Rijeka Europa League form: LLL
HNK Rijeka form (all competitions): WLLLLW
Napoli are without big-money striker Victor Osimhen, who is expected to be out until the turn of the year with a shoulder injury sustained on international duty. Defenders Elseid Hysaj and Amir Rrahmani both tested positive for COVID-19 and remain in quarantine.
Gattuso can welcome back goalkeeper David Ospina, who returns after injury and could replace Alex Meret between the posts, while Andrea Petagna will most likely gain the nod up front as Lorenzo Insigne is rested. In midfield, Tiemoue Bakayoko should start again as he was absent through suspension on Sunday.
Underdogs Rijeka are expected to field a five-man defence at San Paolo, where Sandro Kulenovic and Bosnian forward Luka Menalo - both on loan from Dinamo Zagreb - should be paired in attack, as North Macedonia striker Milan Ristovski is still out with a long-term ankle injury.
If Rozman decides to select a 5-4-1 rather than a two-man forward line, then Robert Muric and Franko Andrijasevic would provide support from out wide for Croatia Under-21 striker Kulenovic.
Napoli possible starting lineup:
Ospina; Di Lorenzo, Maksimovic, Koulibaly, Rui; Bakayoko, Demme, Politano; Mertens, Zielinski; Petagna
HNK Rijeka possible starting lineup:
Nevistic; Tomecak, Escoval, Velkoski, Smolcic, Braut; Muric, Andrijasevic, Loncar; Kulenovic, Menalo
We say: Napoli 3-1 HNK Rijeka
Whichever XI is fielded by Gattuso, Napoli have far too much strength in depth to have concerns about securing another valuable three points on the road towards Europa League progress.
Pointless Rijeka have been further hampered by their lack of recent game time, so can expect to receive similar treatment as when they were utterly dismantled in Alkmaar last month.