A week after their cathartic - if not decisive - defeat of Juventus, Italy's long-time league leaders can become champions by claiming three points and seeing second-placed Lazio fail to win on Sunday.
Match preview
When Giacomo Raspadori's last-gasp winner hit the back of the net in Turin, a surge of relief and joy was released across Naples: despite already leading the Serie A title race by 14 points, victory over the Old Lady somehow seemed to validate Napoli as Italian champions.
Getting one over on their northern counterparts - who twice had the ball in the net during the second half of the teams' Sunday night contest, but were twice denied by the VAR - leaves Luciano Spalletti's men in touching distance of claiming the club's third Scudetto; some 33 years after their last - almost to the day.
With six games to go, it would be the earliest title win ever in terms of games remaining, and despite some recent stumbles Napoli have accumulated 78 points so far, which is just one fewer than the whole of last season.
However, after scoring in 16 consecutive Serie A home fixtures - and at a rate of nearly three goals per game - the Partenopei have failed to score in three of their last four before returning to Stadio Maradona on Saturday.
Only a late Victor Osimhen strike in the Champions League exit to Milan - when it was essentially already too late - has given the Neapolitan faithful much to cheer about in recent weeks, but they will still expect to celebrate in style over the coming days.
Unbeaten in five previous top-flight meetings with Salernitana, if Napoli take care of business this weekend and Lazio then win, they would still ensure glory by beating Udinese next week - regardless of the result between Lazio and Sassuolo.
Determined to spoil their regional rivals' party, Salernitana enter this Campanian derby in their best form of the season - indeed, they are currently enjoying the club's best-ever unbeaten streak in Serie A.
Having avoided defeat for eight games - a run featuring two wins and six draws - the Granata have also put together the longest current unbeaten sequence in Italy's top flight, so they will not simply roll over and watch Napoli celebrate.
During that time, Paulo Sousa's side have drawn each of their last four away games; holding both Milan and Torino, while conceding just three goals in the process.
There is no doubting the impact the Portuguese coach has made in Salerno since succeeding Davide Nicola earlier this year, and last week's 3-0 home victory over Sassuolo leaves his team 14th and some seven points clear of the drop zone.
Securing a third straight season of top-tier football at Stadio Arechi remains in sight then, but having been beaten 4-1 on their last trip to Naples and then 2-0 in January's reverse fixture, the sheer size of their task on Saturday is quite clear.
Napoli Serie A form:
W
W
L
W
D
W
Napoli form (all competitions):
L
W
L
D
D
W
Salernitana Serie A form:
D
D
D
D
D
W
Team News
During their Champions League exit last time out at Stadio Maradona, Napoli saw Mario Rui and Matteo Politano forced off by injury, and while the latter could now return from an ankle sprain, the former is ruled out again.
In better news for Luciano Spalletti - who is on the verge of becoming an Italian champion for the first time, some 553 games into his Serie A career - Giovanni Simeone has recovered from a thigh problem and Amir Rrahmani is available after an ankle injury.
Even if Politano is passed fit, Hirving Lozano should start on the right wing; Mathias Olivera continues to deputise for Mario Rui at left-back and Rrahmani is set to replace Juan Jesus at the heart of the hosts' defence.
While Capocannoniere leader Victor Osimhen spearheads Napoli's attack, Salernitana will turn to Boulaye Dia in search of goals. The Senegal star scored again and laid on an assist in last week's win over Sassuolo, reaching 11 goals and six assists in the league this season.
Elsewhere, Pasquale Mazzocchi recently returned from injury and now faces a battle with Grigoris Kastanos to feature on the visitors' right flank, but Domen Crnigoj and Federico Fazio remain out of action.
Napoli possible starting lineup:
Meret; Di Lorenzo, Kim, Rrahmani, Olivera; Anguissa, Lobotka, Zielinski; Lozano, Osimhen, Kvaratskhelia
Salernitana possible starting lineup:
Ochoa; Daniliuc, Gyomber, Pirola; Mazzocchi, Vilhena, Coulibaly, Bradaric; Candreva, Kastanos; Dia