In his 101st race, the 25-year-old German has a clear goal - to finish in the top four and thereby make it impossible for his only rival Fernando Alonso of Ferrari to overhaul his 13 points deficit and take his own third title.
On paper, for Vettel, it sounds simple enough after a sequence of results that recently saw him reel off four straight wins before finishing third in Abu Dhabi, after starting in the pit lane, and then second in Austin last Sunday.
But he knows that Alonso, 31, and Ferrari will do all they possibly can, within the rules, to seize the Spaniard's first title triumph since he joined the team.
He will be aware, too, of the threat from both McLaren drivers Lewis Hamilton and Jenson Button in the season finale.
Hamilton, in particular, has made it clear he wants to mark the 20th and final race of the year and of his career with McLaren on a high note as he races in their colours for the 110th time before transferring to Mercedes next year.
"Brazil has been the scene of some epic races for me during my time at McLaren and, for many reasons, this weekend will be a very big race for me," said Hamilton, 27.
"As my final race behind the wheel of a McLaren, I vow to the whole team that I'll give it my all on every single lap."
The Briton will know he has the team behind him again, for the last time, as they want to end the season on a high with both drivers on the podium if possible.
That will make life difficult for Vettel and Red Bull whose frailties were exposed last Sunday when Mark Webber had to retire with alternator failure, the team's third in races.
In response, the team are planning to run with updated parts and to attack throughout the weekend.
Even if the weekend turns into a battle for survival in the rain, as forecast, Red Bull have declared they will not be taking a cautious approach.
Team chief Christian Horner said they know no other approach than racing to win.
"We just have to approach the next race as we have the previous 19," he said.
"We have to go there, attack the weekend, and get the best out of ourselves; the car, the strategy, the drivers, and reliability.
"Anything can happen, as we have seen this season, but it is good to be going there with a lead, and we go there determined to close the job off."
Alonso and Ferrari, who demonstrated their pragmatism in Texas by deliberately sacrificing Brazilian Felipe Massa's grid position for the benefit of Alonso, by breaking the seal on his gearbox, are equally focussed on raising their performance for what promises to be an exciting end to a long season.
Team chief Stefano Domenicali said: "Pragmatically speaking, we know that the result has to be better. We have to be in front of Sebastian and we need some drivers in the middle, without thinking of the worst-case scenario.
"And this is the approach that we have to have. We know that it's not easy because he's driving very well and has a very quick car, but that doesn't change what we have to do.
"We have seen that Mark (Webber) had a reliability issue and that can happen every time. But I want to stay concentrated on the job we have to do, and prepare the car in the best way we can."
For Ferrari, it will be critical to improve their qualifying performance at a circuit that has fond memories for Alonso, who won the 2006 title for Renault at Interlagos after a tight duel with old rival Michael Schumacher, then in his last season with Ferrari.
This time around, Schumacher will be retiring again, but now for good, after a lacklustre return in 2010. At 43, and after 306 race starts, he will making his final exit, to be replaced alongside Nico Rosberg by Hamilton.
"My departure will probably be less emotional for me this time than in 2006, when we were still fighting for the championship and everything was much more intense," said Schumacher.
"This time around, I will be able to pay more attention to my farewell and hopefully savour it too.
"I have had fantastic years in Formula One and a lot of support from fans around the world and I wish to particularly thank them for that."
How Sebastian Vettel and Fernando Alonso can win the 2012 title at the season-closing Brazilian Grand Prix on Dunday:
Vettel wins the title if:
- He finishes in the top four
- He finishes fifth, sixth or seventh and Alonso doesn't win
- He finishes eighth or ninth and Alonso is third or lower
- He finishes 10th or worse and Alonso is not on the podium
Alonso wins the title if:
- He wins and Vettel is fifth or lower
- He is second and Vettel eighth or lower
- He is third and Vettel is 10th or lower