The 23-year-old stormed to victory in Sepang last year as McLaren and Ferrari misjudged a rain-hit qualifying session which left them at the back of the grid for the race.
And the German leads the world championship following a dominant weekend at the Australian Grand Prix two weeks ago.
Sepang should also allow drivers to get the best use out of the new Drag Reduction System introduced for the 2011 season, while KERS should also be a prominent feature to boost overtaking for those teams running it.
VettelÃ¢â‚¬â„¢s chances of victory will be increased if Red Bull opt to use KERS after removing it from both cars in Melbourne citing a possible reliability issue.
Despite that, Vettel was still comfortably quicker than McLaren rival Lewis Hamilton in qualifying and the race.
The weather in Malaysia will be key to the weekend with April the hottest month of the year. Stifling heat in excess of 30C coupled with high humidity means downpours are expected once again.
Pirelli will also come under increased scrutiny over its new tyres. Degradation is expected to be much quicker in the hotter temperatures, with three or four pit-stops the norm for most drivers, before additional changes between dry, intermediate and wet tyres if the weather changes.
Sepang is a notable race for many teams this weekend with Mercedes GP backed by the government-owned oil company Petronas, also the title sponsor of the race.
Malaysian entrepreneur Tony Fernandes owns Team Lotus and MalaysiaÃ¢â‚¬â„¢s leading automotive manufacturer Proton funds Renault through its subsidiary Group Lotus.
McLaren will look to build on a solid opening race, where Hamilton finished second to Vettel despite poor performances in winter testing.
But as they chase their first win in Malaysia since 2007, team principal Martin Whitmarsh believes Red Bull could once again be dominant with added pace they did not show at Albert Park.
Ferrari last won in Malaysia in 2008 with Kimi RÃƒÂ¤ikkÃƒÂ¶nen, and the team will be hoping to bounce back from a largely disappointing opening showing and at the very least challenge McLaren and Renault for the second row.
Renault, who showed good pace with Vitaly Petrov in the opening race, will be looking for more of the same from their Russian driver after he secured his maiden podium.
And the team will be hoping Nick Heidfeld can put a disappointing weekend behind him to push the team towards the front-runners.
Mercedes will be particularly keen to impress after an indifferent start to the campaign. And with their technical problems reportedly resolved, in Michael Schumacher they have the most successful driver round Sepang following his three wins with Ferrari in 2000, 2001, and 2004.
Sauber, who finished seventh and eighth in Melbourne before being thrown out of the race for a technical infringement, will look to bounce back and build on their otherwise impressive weekend after their inexperienced pairing of Kamui Kobayashi and Sergio PÃƒÂ©rez showed they arenÃ¢â‚¬â„¢t afraid to take it to the big names.
At the back of the grid Hispania will run their 2011 wing for the first time after passing the FIA crash test, hoping it will allow them to qualify both cars for the first time this season and bring them closer to rivals Virgin and Team Lotus.
Tonio Liuzzi could not quite make it in Melbourne, and should set a qualifying time this weekend. However, Narain Karthikeyan has been massively off the pace of his new team-mate, and could be the only driver to miss out despite talking up a good show before the weekend gets under way.
Team Lotus believe they have resolved the technical issues which have plagued them since winter testing, and after showing good race pace in Melbourne they will expect to be closer to midfield teams Toro Rosso and Force India.
Considering their performance in Malaysia 12 months ago, and their impressive start to the season, it is hard to look beyond another Red Bull victory.
But Sepang has an eventful history, and with several rookies on the grid, KERS, DRS, and unpredictable tyres to factor in, it could be one of the most spectacular races weÃ¢â‚¬â„¢ve had in recent years.
Free Practice 1 for the Malaysian Grand Prix begins at 0300BST on Friday, with qualifying at 0900 on Saturday, and the race also at 0900 on Sunday.
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BIOGRAPHY: Ethan Hazard
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