The 24-year-old German, winner of the European Grand Prix in 2010 and 2011, is gunning for a hat-trick on the streets of the Spanish Mediterranean port city to become the first repeat winner of a season that has turned into one of the most unpredictable on record.
If predictability is to return to the championship, then Valencia is the right place for it.
The driver starting on pole position has won three out of the four races there on a tight and twisty circuit that has acquired a reputation for serving up few thrills and little overtaking.
Vettel has finished off the podium in his last three races, the first time that has happened in the last three years, but reckons the tide has turned.
"We have learned more and will make a step forward in Valencia," he said after finishing fourth in Montreal this month.
McLaren have yet to win in Valencia but championship leader Lewis Hamilton, winner in Canada, is the bookmakers' favourite.
Whether he will convert that into two successive victories is anyone's guess, with all the teams struggling to understand the tyres fully.
"People are always asking me to predict what will happen at the next race and I always tell them it's really difficult to make an accurate prediction," said the 2008 world champion who leads Ferrari's local hero Fernando Alonso by two points.
"But I'll be heading to Valencia feeling super-motivated to get another strong result and maintain my momentum before we head into Silverstone and the British Grand Prix."
Seven times champion Schumacher, who has not stood on the podium since he retired from Ferrari in 2006 and then began his comeback in 2010, has a winning car but also a streak of bad luck that Mercedes are desperate to end.
Raikkonen has been on the podium for Lotus but Grosjean, second in Montreal and third in Bahrain in his first full season, has looked more likely to take the big step up.
The Lotus has also thrived in hot conditions.
"I made my Formula One debut here in 2009, so it brings back good memories and it's a circuit I like anyway," said Grosjean. "It's a circuit that could suit us quite well.
"If we have a strong weekend from the start then I think we are capable of fighting for a podium or even a win."
Sauber's young Mexican Sergio Perez has also been on the podium twice this season and could have won in Malaysia.
Alonso's team mate Felipe Massa must also be mentioned as winner of the first race in Valencia in 2008, even if the Brazilian has not been on the podium since 2010 or looked close to doing so this season.
He seemed more comfortable in the car in Canada, however.
"It's true, I'm much happier because I can drive the F2012 much more in the way I like now," he told the team website (www.ferrari.com).
"It always puts you in a positive frame of mind coming to a place where you have won before. So, I hope we can have another good weekend this time, especially given the fact our car is now more competitive in the races and also in qualifying."