With four games to go, the visitors are embroiled in a fierce battle for a place in the Champions League, while their hosts are on a four-game winless streak which imperils their survival - despite an impressive debut Serie A campaign.
Having fallen two points behind fellow top-four contenders Juventus, Milan and Atalanta, after a 1-1 draw with relegation battlers Cagliari last weekend, Napoli need to get back to winning ways on Saturday against a struggling Spezia side.
Although in their last 11 games Gennaro Gattuso's men have posted eight wins, three draws and only one defeat - against Juventus, in a belatedly rescheduled autumn fixture - the pace has been set ferociously high, and they will therefore seek to impose historical superiority over the modest Ligurian outfit.
The Partenopei have won six of their last seven games against Spezia in all competitions and, though they surprisingly lost the reverse fixture in January, the most recent meeting between the two clubs was a 4-2 Coppa Italia quarter-final success just weeks later.
Club record signing Victor Osimhen was only a peripheral figure on both occasions, but has since regained a starting place and scored Napoli's goal last time out - though they were later denied maximum points by Cagliari's late equaliser.
Showing further signs of getting back to his best after struggling to make an impact in the first half of the season due to injuries and illness, Osimhen's joy at notching an eighth goal in just 12 league starts this season was blighted only by being forced off injured in the second half - but the Nigeria international now looks set fair for a productive conclusion to the campaign.
Alongside him up front, inspirational captain Lorenzo Insigne (17 goals) is currently a single strike shy of matching his best-ever goalscoring season and has a well-earned reputation as something of a specialist against Calcio's lesser lights, having been involved in 15 goals in his last 13 games against promoted sides.
Thanks in part to the pair's penalty-box potency since the turn of the year, Napoli have now scored in each of their last 22 league games - only in 1975 (with 24) have they netted in more consecutive matches in their top-flight history. Furthermore, ahead of their trip to La Spezia, Gattuso's side have stayed disciplined in defence, as they have not conceded a goal in four of their last five away games.
Though Spezia seemed a solid bet to retain their hard-won Serie A status after an eye-catching first half of their debut season in Serie A, recent form - including a current streak of one point from a possible twelve - has seen the Aquilotti's drop fears renewed.
Highly-regarded coach Vincenzo Italiano has seen his team slide to 16th in the standings - on equal terms with Torino, who still have a game in hand - and now just three points clear of 18th-placed Benevento.
Having surprised many with their ability to pick up points from unlikely places - such as at Stadio Maradona, versus Napoli, and against both Milan clubs - the Ligurians are now in danger of demotion back to the second tier at the end of the month.
After Saturday's challenging task at the Picco, Spezia must also take on direct rivals Torino, then mid-table Sampdoria, before hosting a wounded Roma side on the final day of the campaign.
Unbeaten in their last six home games, however, the Bianconeri will enjoy home advantage in three of their final four outings - a potentially skin-saving quirk of the fixture list.
Napoli coach Gennaro Gattuso will have to manage without some integral elements of his defense on Saturday, as central defenders Kalidou Koulibaly (thigh) and Nikola Maksimovic (COVID-19) have been ruled out of action. In addition, first-choice goalkeeper David Ospina remains sidelined with a thigh strain - though the former Arsenal man is expected to make his return in the coming days.
Longer-term injury absentees Stanislav Lobotka and Faouzi Ghoulam will miss the rest of the season, as Alex Meret continues to deputise for Ospina and will most likely line up with Kostas Manolas and Amir Rrahmani forming the centre-back pairing in front of him.
Central midfielders Nahuel Estevez, Leo Sena and Tommaso Pobega are in direct competition for one available space in the Spezia engine room, while on-loan forward Riccardo Saponara can push for a rare start following his goal at Verona last time out, as Diego Farias is still doubtful.
Up front, Nzola's absence should be covered by promising striker Roberto Piccoli.
Spezia possible starting lineup:
Provedel; Vignali, Erlic, Ismajli, Marchizza; Estevez, Ricci, Maggiore; Verde, Piccoli, Gyasi
Napoli possible starting lineup:
Meret; Di Lorenzo, Manolas, Rrahmani, Rui; Demme, Ruiz; Lozano, Zielinski, Insigne; Osimhen
We say: Spezia 1-3 Napoli
Although Spezia are a tougher proposition on home soil, free-scoring Napoli can exploit their defensive deficiencies to take maximum points from an important fixture for both sides.
Thanks to their diverse attacking options, the Partenopei can gain a measure of revenge on their Ligurian hosts - who beat them at the Maradona - while staying in the hunt for a place at Europe's top table next term.