While the hosts, who are aiming to go one better after finishing runners-up last term, escaped with a last-gasp win at Lecce, their Ligurian counterparts won 1-0 at home to kick off the club's third top-flight campaign.
Match preview
It may have required the last kick off the game to get them there, but Inter began their quest to regain the Scudetto with a victory last weekend, as substitute Denzel Dumfries turned in a stoppage-time winner to bookend Romelu Lukaku's second-minute opener.
In between, the Nerazzurri controlled large swathes of the game at Lecce's Stadio Via del Mare, so Simone Inzaghi was understandably relieved to claim a merited three points at the final whistle.
After finishing second to Milan in May, Inter moved quickly to bring Lukaku back to the club, and the Belgian striker has already rekindled his potent partnership with Lautaro Martinez up front.
This week, though, the man once adored by the Nerazzurri faithful must face the fans he spurned shortly after lifting the Scudetto in 2021, as he strides out again at San Siro, where Inter have lost only two of their last 36 league matches.
Stretching back to the end of last season, Inzaghi's men have also won nine of their last 10 in Serie A - though the one defeat in that sequence effectively cost them the title - and their record against Saturday's visitors is unsurprisingly impressive.
Inter are unbeaten in all six of their previous encounters with Spezia in either Serie A or the Coppa Italia, incorporating five wins and one draw - scoring 16 goals and conceding only four in the process.
Beaten 2-0 by Inter at San Siro last year, and then 3-1 at home, Spezia have lived up to their role as underdogs in meetings with their second opponents of the new Serie A season, but they arrive in Milan level on points with their more revered rivals - albeit that tally stands at a modest three.
Luca Gotti's side kicked off the 2022-23 campaign positively, with a 1-0 win over Empoli last Sunday, as M'Bala Nzola finally broke his long goalscoring drought in the Italian top flight.
The Angolan forward's first-half strike decided a closely contested game at Stadio Alberto Picco, and Gotti will have been relieved to get the better of a possible relegation rival on his debut in the Spezia dugout.
Having secured a third straight season in Serie A - to which they ascended for the first time in 2020 - by a six-point margin last term, the Ligurian outfit will seek mid-table security this time around.
Starting with successive wins bodes well in that regard - Spezia crushed Como 5-1 in the first round of the Coppa Italia earlier this month - but now the Aquilotti tackle one of the toughest tests in Calcio.
Inter Milan Serie A form:
Inter Milan form (all competitions):
Spezia Serie A form:
Spezia form (all competitions):
Team News
After spending the summer restocking for the challenges ahead, Simone Inzaghi will have something of a selection headache to deal with on Saturday, as he has an almost fully fit squad following the return of Danilo D'Ambrosio.
Only Henrikh Mkhitaryan remains out of commission, and the thigh injury that keeps the ex-Roma playmaker sidelined could even threaten his participation in the Milan derby at the start of September.
Ivan Perisic and Alexis Sanchez are among several players to have departed since last season, and the former's switch to Spurs sees Robin Gosens lining up on the left flank of the hosts' 3-5-2 formation. Meanwhile, Federico Dimarco will hope to keep his place on that side of the back three, ahead of Alessandro Bastoni.
Spezia are yet to secure a replacement for deposed captain Giulio Maggiore, who has refused to play after being replaced as skipper by Emmanuel Gyasi, as a result of declining a new contract.
Gyasi is likely to start on the right wing for the visitors, while M'Bala Nzola leads the line up front - against Empoli, the latter finally scored in Serie A for the first time since last November.
Aimar Sher's return from injury offers Gotti another option in midfield, alongside summer signing Albin Ekdal, who started last week's win on the bench. However, he is set to be without the services of Janis Antiste, Kelvin Amian, Salva Ferrer and Viktor Kovalenko once again.
Inter Milan possible starting lineup:
Handanovic; Skriniar, De Vrij, A. Bastoni; Dumfries, Barella, Brozovic, Calhanoglu, Gosens; Martinez, Lukaku
Spezia possible starting lineup:
Dragowski; Caldara, Kiwior, Nikolaou; Gyasi, Bourabia, Ekdal, S. Bastoni, Reca; Verde, Nzola