After two tough losses in the past week, the Partenopei now take on Vincenzo Italiano's side in the quarter-finals, with the visitors intent on staying in contention for a first cup win in their modest history.
The bitter sting of last week's loss to Juventus in the Supercoppa Italiana had barely subsided for Napoli when they ventured to Verona at the weekend, with Gennaro Gattuso's side sent home reeling after a comprehensive 3-1 defeat.
Seeing their Serie A form waning somewhat since the turn of the year, the Azzurri now sit sixth in the tightly-packed top half of the table and are nine points off top spot - albeit with a game in hand on most sides around them.
Gattuso, who has yet to agree a new contract with the club's similarly fiery president Aurelio de Laurentiis ahead of his current deal's expiry in the summer, has seen his position come under scrutiny, with some observers making a logical link to the recent availability of the club's former boss Rafa Benitez.
Nonetheless, the ex-Milan manager will now continue his quest for more silverware with a home tie against Spezia in the Coppa Italia, before hosting lowly Parma in Serie A next Sunday.
A potential semi-final versus Atalanta or Lazio awaits if Napoli can negotiate their way past their Ligurian opponents, who emerged triumphant from the clubs' first meeting this season - a shock 2-1 Spezia success at the Maradona earlier this month.
That match marked the start of a run of six games in which Napoli have conceded a total of 10 goals - not a flood by any means, but well out of keeping with their previously league-leading defensive stats. Gattuso's primary task, then, will be to tighten up at the back - particularly as Thursday's visitors are on form in front of goal.
Spezia convened with previous opponents Roma twice in four days: first to decide who would meet Napoli in the Coppa quarters, then in the 19th round of Serie A - with both games hosted in Rome. On each occasion, goals flowed freely - Spezia's eventful 4-2 extra-time win in the cup was swiftly followed by an even more dramatic 4-3 defeat in Serie A.
Even though Vincenzo Italiano's plucky outfit were downhearted at missing out on a point on Sunday - after pulling the scoreline back to 3-3 through goals from Diego Farias, Roberto Piccoli and Roma primevera product Daniele Verde, before ultimately conceding the decisive goal to Lorenzo Pellegrini in stoppage time - they should also gain confidence from their impressive adaptation to life at the top level.
The Bianconeri had previously performed heroics to earn a point away to Torino after going down to ten men in the eighth minute, which followed two successive Serie A wins - against top-half sides Napoli and Sampdoria. All of which leaves them 14th in the standings and very much in contention to avoid a swift return to Serie B.
Therefore, attack-minded coach Italiano may well throw caution to the wind against Napoli, sensing an under-pressure home side could be vulnerable to his team's admirably progressive approach. However, only one clean sheet in their last 13 matches in all competitions tells the tale of Spezia's eminently breachable back line.
Having many of the ingredients of a good cup side though, they arrive in Naples with nothing to lose and perhaps everything to gain.
Wins over Citadella, Bologna (after extra time) and then mighty Roma in the previous rounds have now brought a once-humble club into the limelight of another glamorous cup clash - with the final four now in touching distance for one of Calcio's biggest overachievers.
Napoli Coppa Italia form: W
Napoli form (all competitions): LWWWLL
Spezia Coppa Italia form: WWW
Spezia form (all competitions): LWWDWL
Despite a packed fixture list - with a return to Europa League duty on the distant horizon - Napoli coach Gennaro Gattuso is expected to field a relatively strong side in defence of the trophy he led them to last summer.
Midfielder Fabian Ruiz will be unavailable due to COVID-19, but otherwise the home side have a full squad to choose from - with forwards Dries Mertens and Victor Osimhen recently returning to action and now vying with each other for a place in the XI.
Spezia are unlikely to rotate as much as they did in the last round - though that policy proved effective, with several squad players coming to the fore.
Lithuanian goalkeeper Titas Krapikas is expected to feature in goal - in place of first choice Ivan Provedel - while in midfield, Matteo Ricci has overcome COVID-19 and may replace loanee Lucien Agoume.
Andrey Galabinov is set to lead the attack, given Roberto Piccoli's injury sustained at the weekend and top scorer M'Bala Nzola's continuing struggles with an ankle problem. Goalscoring hero in the last-16 Riccardo Saponara is also a doubt, so Daniele Verde should start on the right.
Napoli possible starting lineup:
Ospina; Di Lorenzo, Manolas, Koulibaly, Rui; Demme, Bakayoko; Lozano, Zielinski, Insigne; Osimhen
Spezia possible starting lineup:
Krapikas; Vignali, Erlic, Chabot, Bastoni; Pobega, Ricci, Maggiore; Verde, Galabinov, Farias
We say: Napoli 2-1 Spezia
A much tougher call than it may first look on paper, Napoli should sneak through due to their cup pedigree and determination to bounce back from recent disappointments.
This would be the year, if there ever was one, that Spezia could feasibly dream of going all the way to a first-ever Coppa Italia final, but defensive deficiencies are set to be ruthlessly exposed by Lozano, Insigne and company on Thursday.