While Inter will be aiming to retain top spot this season, their hosts are intent on breaking into Italy's top 10.
Match preview
Securing a 20th Scudetto - and a second star on their famous black-and-blue jersey - Inter wrapped up last term's title in the sweetest style possible, beating city rivals AC Milan at San Siro.
Even after drawing their final two fixtures, the Nerazzurri could boast a mammoth 19-point gap over Milan in the final standings, which was the second-biggest difference between first and second throughout Italy's three-points-per-win era, also surpassing Napoli's feats of one year earlier.
Irrepressible captain Lautaro Martinez linked up wonderfully with Marcus Thuram and was crowned Capocannoniere with 24 goals from 33 league appearances, before taking his place in the Argentina squad that retained the Copa America.
With few changes to last season's dominant squad, head coach Simone Inzaghi oversaw a busy summer itinerary, with Inter drawing their final friendly 1-1 against Chelsea on Sunday.
Now, a side that lost just one league game on the road in 2023-24 travels to Liguria, where they will aim to maintain recent precedent among reigning Serie A champions: the Scudetto holders have won their first match in 12 of the last 13 Serie A seasons.
Furthermore, Inter have outscored Saturday's hosts by an aggregate score of 28-2 during an ongoing unbeaten streak that stands at 10 top-flight meetings between them.
In a rare case of two coaches remaining in-post following a managerial merry-go-round in Italy this summer, Genoa boss Alberto Gilardino will reconvene with Inzaghi this weekend.
The former Milan striker - who played with Simone's brother Pippo Inzaghi while at San Siro - is looking forward to his second full season in charge, having led the Grifone back to Serie A after being appointed in December 2022 and then kept them up with room to spare last season.
Genoa's resilience served them well during their comeback campaign, as they gained no fewer than 18 points from losing positions - a club record since the top flight returned to 20 teams back in 2004.
As a result, relegation was never a concern, and Gilardino's men put the full stop on a solid mid-table finish with a final-day win over Bologna.
Only beaten five times at Marassi in 2023-24, the Rossoblu now begin a new league campaign at their inimitable home stadium, where they beat Reggiana 1-0 in the Coppa Italia last Friday.
However, the last time Genoa took three points off this week's visitors came as far back as 2018, when ex-Inter striker Goran Pandev was on target in a 2-0 victory.
Genoa form (all competitions):
Inter Milan pre-season form:
Team News
Inter's main summer signing Mehdi Taremi - who scored five goals in three pre-season friendlies before suffering a thigh injury - should be available after returning to training, but the champions will be without several other players on Saturday evening.
Simone Inzaghi is unable to call upon another new boy, Piotr Zielinski, plus Stefan de Vrij, Tajon Buchanan and Marko Arnautovic.
Even with ex-Porto star Taremi back in the fold, the visitors should turn to the familiar strike partnership of Marcus Thuram and Lautaro Martinez to lead their attack.
Notably, among the 29 opponents he has faced so far in Serie A, Genoa are one of only two against whom the latter has not yet scored; however, 'El Toro' has been involved in five goals in his last four season-openers.
Meanwhile, Genoa must start the season with a new number one, as Josep Martinez joined Inter earlier this summer, to provide competition for Yann Sommer; either Pierluigi Gollini or Nicola Leali will feature between the posts.
Frequently linked to the Nerazzurri following his stellar 14-goal campaign last term, Albert Gudmundsson is still with the Grifone for now, but as speculation rages, he may be consigned to the bench.
Former partner Mateo Retegui has left for Atalanta BC, so Vitinha and Junior Messias - the latter of whom netted Genoa's winner in the cup last week - could form a makeshift front pairing.
Genoa possible starting lineup:
Gollini; De Winter, Bani, Vasquez; Sabelli, Frendrup, Badelj, Thorsby, Martin; Messias, Vitinha
Inter Milan possible starting lineup:
Sommer; Pavard, Acerbi, Bastoni; Dumfries, Barella, Calhanoglu, Mkhitaryan, Dimarco; Thuram, Martinez