Ultimately aiming to lift the trophy for a 10th time, Inter must first beat the Biancocelesti if they are to play AC Milan in the final four.
Match preview
An eventful February so far has seen Inter draw the Milan derby, suffer a 3-0 defeat in Florence and lose the Derby d'Italia to Juventus - but they have also beaten both Fiorentina and Genoa at San Siro.
A late goal from captain Lautaro Martinez saw off Genoa, as the Nerazzurri seized top spot in Serie A: Napoli's subsequent loss to Como leaves them with a one-point lead before Saturday's high-stakes showdown in Naples.
Though they lost last month's Supercoppa Italiana final to their city rivals, a potential treble is still possible for Simone Inzaghi's side this season.
Inter not only have their noses ahead in the Scudetto race but are also set to meet Milan's conquerors Feyenoord in the Champions League's last 16, and now the nine-time winners continue their latest Coppa Italia campaign.
As usual, they came in at the round-of-16 stage due to European commitments, and first-half goals from Marko Arnautovic and Kristjan Asllani saw them beat Udinese.
Inzaghi now tackles his old club - who he first played for and then managed a club-record 197 times in Serie A, recording 108 wins in the process - having overseen an incredible six-goal success when the teams last met.
Amid their best run of form this season, Lazio were abruptly stopped in their tracks by Inter midway through December, when they slumped to a 6-0 defeat at Stadio Olimpico.
The capital club have won just two of the last nine league meetings with their second-city counterparts, who have held the upper hand since snaring Inzaghi.
Like their quarter-final hosts, Lazio were also handed a bye to the last 16, before beating Napoli 3-1 via a Tijjani Noslin hat-trick.
The seven-time Coppa Italia winners have since strolled through to the Europa League knockout phase, and they will soon vie with Viktoria Plzen for a last-eight place in that competition.
First, Marco Baroni's men aim to conquer Inter and book a return to San Siro in April, when they would meet Milan in a two-legged semi-final.
Top-four contenders in Serie A, the Biancocelesti come into this tie after back-to-back league draws - with Napoli and Venezia - so they must now step up a gear to beat the Italian champions.
Inter Milan Coppa Italia form:
W
Inter Milan form (all competitions):
W
D
L
W
L
W
Lazio Coppa Italia form:
W
Lazio form (all competitions):
L
L
W
W
D
D
Team News
Already without first-choice goalkeeper Yann Sommer - who underwent thumb surgery last week - and French forward Marcus Thuram, Inter boss Simone Inzaghi has a new injury concern regarding Thuram's replacement against Genoa.
Ex-Lazio striker Joaquin Correa was only able to play the first half after suffering a knee sprain, so either Marko Arnautovic or Mehdi Taremi must fill in; furthermore, Carlos Augusto and Davide Frattesi are still doubts.
With a potential title decider coming up on Saturday, Inzaghi may make further changes: Stefan de Vrij, Piotr Zielinski and Hakan Calhanoglu are all contenders for promotion from the bench.
Meanwhile, Lazio are still missing top scorer Taty Castellanos through injury - meaning Coppa hat-trick hero Tijjani Noslin could continue up front - but influential midfielder Nicolo Rovella is back after a one-match ban.
Elseid Hysaj and former Inter midfielder Matias Vecino join Castellanos on the sidelines, while Fisayo Dele-Bashiru picked up a knock against Venezia and may also miss out.
It remains to be seen whether Ivan Provedel will return after being dropped on Saturday; cup goalkeeper Christos Mandas took the gloves at Stadio Penzo, but Marco Baroni has since stated that Provedel remains his number one.
Inter Milan possible starting lineup:
J. Martinez; Bisseck, De Vrij, Bastoni; Dumfries, Barella, Calhanoglu, Zielinski, Dimarco; L. Martinez, Taremi
Lazio possible starting lineup:
Mandas; Lazzari, Gila, Romagnoli, Tavares; Guendouzi, Rovella; Isaksen, Pedro, Zaccagni; Noslin
We say: Inter Milan 2-1 Lazio (after extra time)
Although Lazio have proven their prowess in the Europa League, they generally come up short against Inter and may make a last-eight exit from the Italian cup.
Written by
Jonathan O'Shea