Last season's Scudetto winners are set to pass the baton on to distant leaders Inter, who sit 16 points clear at the summit after 10 league wins on the spin.
Match preview
Bringing their perfect record for 2024 to a shuddering halt, Inter crashed out of the Champions League on Wednesday, after a 2-1 defeat to Atletico Madrid was followed by failure in a tense penalty-shootout.
Federico Dimarco's opener had put the Nerazzurri two goals ahead on aggregate, but after conceding twice, last year's beaten finalists could not produce a response during extra time in the Spanish capital, before Lautaro Martinez blasted his decisive spot-kick over the crossbar.
Also out of the Coppa Italia, all that remains for Simone Inzaghi's men is the formality of wrapping up the Italian title over the weeks ahead: Inter are in a surely unassailable position ahead of old foes AC Milan and Juventus.
They now resume domestic duty seeking an 11th consecutive league win for just the third time in their long history, having posted 17 in the 2005-06 season and then 11 under Antonio Conte three years ago.
Though they will not be crowned kings of the continent, Inter have still scored 70 top-flight goals while conceding just 13, which is not only the best goal difference across Europe's top five leagues but also the best for a Serie A side at this stage of a season since the 1950s.
Having also won seven of their last 11 league matches against Napoli, including December's reverse fixture - a 3-0 success at Stadio Maradona - the Milan giants will expect to get straight back on track this weekend.
Beating Inter out of the Champions League exit door by one day, Napoli succumbed to Barcelona at Montjuic, losing 3-1 on the night and 4-2 on aggregate.
After last term's quarter-final debut, the Partenopei were eliminated in the first knockout round for a fourth time in five attempts - but expectations were relatively low, given how their season has unfolded.
Even after a recent revival under new management, Napoli are no fewer than 31 points adrift of Inter in the Serie A standings, and their tame defence of the Scudetto petered out before it really started.
Current coach Francesco Calzona returned to Naples just days before last month's first-leg meeting with Barca, becoming the Campanian club's third boss of the season, but with reigning Capocannoniere Victor Osimhen now available and Khvicha Kvaratskhelia returning to form they are back in the mix for European qualification.
Just one loss from six since Calzona took the reins, featuring five goals from Osimhen and four from Kvaratskhelia, has helped steady the ship, and the latter scored the opener in a 1-1 draw with Torino last Friday.
While they have averaged 2.5 goals per game during that time - one more than in 12 league matches overseen by Walter Mazzarri - Napoli now visit San Siro, where they have lost all of their last five league meetings with Inter by an aggregate score of 8-2.
Inter Milan Serie A form:
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Inter Milan form (all competitions):
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Napoli Serie A form:
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D
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Napoli form (all competitions):
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Team News
After 120 minutes of intense action in Madrid, Simone Inzaghi is sure to make changes on Sunday evening, when Davide Frattesi and Yann Bisseck could both be promoted to Inter's starting lineup.
While Marko Arnautovic, Juan Cuadrado and Stefano Sensi are still unavailable, Brazilian wing-back Carlos Augusto should return from a muscular injury after missing the midweek trip to Spain.
If he can recover from his penalty heartache, captain Lautaro Martinez will try to score the goal that would see him score 10 times at home in each of the last four seasons, a tally only Erling Haaland has recorded across Europe's top five leagues during that period.
With one more goal, midfield maestro Hakan Calhanoglu - who scored in Naples earlier this season - will reach double figures for just the second time in his career, having previously netted 11 for Hamburg a decade ago.
Meanwhile, Napoli's main marksman Victor Osimhen is a fitness doubt, so Giovanni Simeone will be on standby to start against his father's former club.
Jens Cajuste and Cyril Ngonge recently returned from thigh injuries, while Piotr Zielinski - who could be bound for Inter this summer - is available again, having been left out of the Partenopei's post-Christmas Champions League squad.
Inter Milan possible starting lineup:
Sommer; Bisseck, Acerbi, Bastoni; Darmian, Barella, Calhanoglu, Frattesi, Dimarco; Thuram, Martinez
Napoli possible starting lineup:
Meret; Di Lorenzo, Rrahmani, Jesus, Olivera; Anguissa, Lobotka, Traore; Politano, Osimhen, Kvaratskhelia