Two weeks after a dramatic tyre failure ended his hopes of a podium finish at the Belgian Grand Prix, the four-time champion German aims to emulate the 56-year-old achievement of Briton Stirling Moss who triumphed in 1956, 1957 and 1959 with Maserati, Vanwall and Rob Walker Racing.
Vettel claimed his maiden Formula One win at the famous old Autodromo Nazionale with the Toro Rosso team in a downpour in 2008 and then won twice more with Red Bull in 2011 and 2013.
Now, he seeks to add a memorable victory on home soil for the scarlet scuderia at a time when the team and their local race, not to mention F1's Italian tyre suppliers, badly need a boost.
In the wake of his angry departure from Spa-Francorchamps, Vettel clarified his emotional criticism of tyre-suppliers Pirelli.
"Just to make things clear," he said in a statement. "The team and I decided our strategy for the race together. I support the team and the team supports me, and this is what makes us a team. Our strategy was never risky, at any point. The team is not to blame.
"We deserved to finish on the podium, but that's racing. A different thing though is not to finish the race because of what happened. This is not easy to accept for a driver, even if it's not as bad as in Silverstone a few years ago.
"But still we need to talk to each other as it can't happen without prior notice."
This ongoing Italian argument - Pirelli have pointed at the team's one stop strategy as risky - ensures an emotional backdrop to highly-charged weekend as the defending double world champion Briton Lewis Hamilton seeks to repeat his 2014 victory and stay in control of the title race.
He currently leads his Mercedes team-mate German Nico Rosberg, who became a father for the first time last weekend, by 28 points.
Hamilton, however, may not find events unfold entirely to his liking at the fastest circuit of the year where it is notoriously difficult for any driver to win twice in succession.
The last to succeed was Briton Damon Hill for Williams in 1993 and 1994 and, before him, Brazilian Nelson Piquet, also for Williams, in 1986 and 1987. They are the only two to do so in 30 years.
Add to that statistical challenge the fact that Rosberg will be desperate to take pole position and has been fired up by his own tyre-failure experience at Spa-Francorchamps.
"Vettel blowing up his tyre, that's really not acceptable," said Rosberg. "For either of us - for me on Friday or for him - if that would have happened a couple of metres earlier or later we would have had huge shunts, I mean the biggest shunts ever, because the track is just so fast.
"The next track is Monza, the fastest track of the year, so they have to think of something to try and improve that situation."
Pirelli hope to defuse a tense situation at Monza. Racing boss Paul Hembery said: "We have finalized the investigation into Sebastian Vettel's tyre at Spa. Detailed conclusions from the technical analysis will be presented at Monza."
Against this backdrop, Ferrari plan an engine upgrade for more power in its race to catch Mercedes.
"We are working, but in Monza there will not be a "super engine," said team chief Maurizio Arrivabene. "We could spend some tokens, but they will be very few. It is not worth talking about a super power unit, but just an engine.
"This is not to say that we will throw in the towel and run away. We will do our best, but we know we go there not being the team to beat."
As Ferrari seek a resurgence on track, the future of the Italian race remains in the balance following comments by the sport's ringmaster Bernie Ecclestone in which he said he "hopes we don't lose it..."
Monza's current deal with Ecclestone ends next year and talks about a new deal have stalled several times.
The track has been on the F1 Championship calendar every year, but one, since 1950. It was replaced by Imola in 1980 and is the most used venue in the sport's history.