Now expected to take another step towards a record-extending 14th cup triumph in the spring, the Bianconeri enter this home tie as undisputed favourites against a side demoted from the top flight last season.
Ahead of their return to Coppa duty, Juventus have been buoyed by two successive 2-0 wins since their Derby d'Italia disaster against Inter.
Juve's barely deserved Supercoppa Italiana victory over Napoli gave under-pressure coach Andrea Pirlo his first silverware since taking charge and they followed that up with a win over Bologna - goals coming from midfielders Arthur and Weston McKennie - to narrow the gap on the league-leading Milan clubs in Serie A.
Now all thoughts turn to securing a showpiece semi-final with one of their rivals from the second city - to be played next week - by taking care of business versus lower-league opposition.
Pirlo's side scraped past Genoa in the last 16, thanks to the unlikely extra-time intervention of Tunisian international Hamza Rafia - a former Lyon youth graduate making his first-team debut as a substitute. This week, they will aim for a more serene route to the final four - even if Pirlo is expected to rotate his resources in the light of an ongoing flurry of fixtures.
Nonetheless, the Bianconeri's squad depth - at least at domestic level - is undoubted and was proven in the league win over Milan earlier this month. Whichever XI their understated coach fields at the Allianz Stadium, he will be confident of brushing aside their relatively modest Emilian visitors.
As undisputed underdogs, SPAL meet their illustrious opponents in the knowledge that success is improbable, but with fond memories of the two sides' Serie A clashes in recent times. Building on earning a goalless draw the season before, the Ferrara-based outfit remarkably turned over the Turin giants 2-1 in April 2019 - with current captain Sergio Floccari netting the winner.
As a barometer of that heroic lineup's individual quality, several members of the team that day are currently Serie A mainstays at their new clubs, including Udinese's Kevin Bonifazi, Manuel Lazzari and Mohamed Fares of Lazio, and Napoli striker Andrea Petagna. However, relegation followed just over a year later.
SPAL's rebound from finishing dead-last at the end of a difficult 2019-20 campaign has been commendable though, as the Biancazzurri are in the mix for promotion straight back from Serie B.
A squad peppered with borrowed talents such as Inter tyro Sebastiano Esposito and Fiorentina's Luca Ranieri have fared well under the guidance of former Udinese coach Pasquale Marino and were good value for their shock win against Sassuolo in the last 16.
Once Coppa runners-up in 1962 but never winners, the Ferrarese began their journey to the final eight at the end of September - eliminating Bari and Crotone (both on penalties) and then moneyed Monza in the previous rounds.
Having warmed up for the cup with a 1-1 league draw against Cremonese on Sunday, this week they take a significant step up in class, as they face the Coppa Italia's most-decorated club - and a star-filled squad who may just be running into form.
SPAL Coppa Italia form: WWWW
SPAL form (all competitions): LLWWWD
Juventus Coppa Italia form: W
Juventus form (all competitions): WWWLWW
Given a never-ending merry-go-round of fixtures - with two matches every week - home coach Andrea Pirlo is likely to take this opportunity to rest some weary limbs.
Veteran defensive pair Leonardo Bonucci and Giorgio Chiellini could potentially both sit out, now that Merih Demiral and Matthijs de Ligt have returned to fitness. Certainly, goalkeeper Gianluigi Buffon is likely to deputise for Wojciech Szczesny and Cristiano Ronaldo may even be offered a rare break, with Alvaro Morata joining Dejan Kulusevski - suspended for next week's league action - up front.
SPAL boss Pasquale Marino is expected to pair experienced duo Alberto Paloschi and Sergio Floccari at the top of his 3-5-2 formation, with on-loan Atalanta striker Marco Tumminello still out injured, though switching to 3-4-2-1 is a possible alternative.
Former Lazio goalkeeper Etrit Berisha returned to the side in the previous round after being hospitalised with COVID-19 at the turn of the year and could have a busy 90 minutes as SPAL's last line of defence.
SPAL possible starting lineup:
Berisha; Tomovic, Vicari, Ranieri; Dickmann, Valoti, Missiroli, Esposito, Sala; Paloschi, Floccari
Juventus possible starting lineup:
Buffon; Cuadrado, De Ligt, Demiral, Frabotta; McKennie, Ramsey, Rabiot, Chiesa; Kulusevski, Morata
We say: Juventus 2-0 SPAL
A third successive win and clean sheet could be in store for Juventus on Wednesday, as they should secure passage to the semis without hitting top gear.
Should the Bianconeri run into trouble at any stage, a well-resourced cavalry is available on the sidelines - with fringe players keen to make an impression ahead of the upcoming return of the Champions League.