Korean champions FC Seoul face the biggest test after losing 3-1 to Al Ittihad in Saudi Arabia their quarter-final first leg two weeks ago, while Jeonbuk must overturn a one-goal deficit after being edged out 4-3 by Japan's Cerezo Osaka in a thrilling tie on September 14.
And with either FC Seoul, Al Ittihad, Jeonbuk or Cerezo set to host November's final, there is added incentive to secure a place in October's semi-finals.
Iran's Sepahan also take a slender one-goal advantage to Doha to face Qatari qualifiers Al Sadd, while Zobahan's tie with Suwon Samsung Bluewings is finely balanced following a 1-1 draw in Korea.
After dispatching Japan's Kashima Antlers 3-0 at home in the Round of 16, FC Seoul will look to build on Choi Tae-uk's potentially crucial first leg strike at FC Seoul World Cup Stadium on Tuesday.
Goals from Mohammed Noor and Osama Al Harbi put 2004 and 2005 champions Al Ittihad in a strong position with 14 minutes remaining at Prince Abdullah Al Faisal Stadium before substitute Choi struck seven minutes later, although Brazilian midfielder Wendel Geraldo was able to restore Al Ittihad's two-goal cushion in stoppage time.
Al Ittihad, though, will look to bounce back from losing 1-0 to Ettifaq in the Saudi League last Tuesday in their last outing before heading to Korea.
Despite letting slip the lead on three occasions against tournament debutants Cerezo, 2006 champions Jeonbuk are still in a strong position to advance to the last four ahead of Tuesday's second leg at Jeonju World Cup Stadium.
Jeonbuk had taken the lead three times at Nagai Stadium through Lee Dong-gook's first half double and a second half strike from Cho Sung-hwan, but after Ryuji Bando, Hiroshi Kiyotake and Kim Bo-kyung hit back on each occasion for the home side, Kiyotake scored his second of the night with nine minutes remaining.
Kiyotake further underlined his importance for Cerezo after playing a central role as Japan beat Malaysia 2-0 in last week's qualifier for the 2012 Olympic Games after also catching the eye for the full national team in August's friendly win over Korea Republic.
Zobahan, meanwhile, are also in a strong position to follow up last year's final appearance after returning from their trip to Suwon with a 1-1 draw ahead of Wednesday's second leg at Foolad Shahr Stadium.
Mohammad Ghazi had opened the scoring the visitors just before the hour at Suwon World Cup Stadium, only for Park Hyun-bem to keep Suwon in the hunt to better last year's run to the last eight.
But while Zobahan are favourites to advance, Mansour Ebrahimzedah's side were worryingly held to a fourth consecutive draw by Shahin Bushehr in the Iran Pro League last Wednesday.
Finally, qualifiers Al Sadd entertain a Sepahan side who will be out to defend the 1-0 win they claimed in Isfahan, although the Iran Pro League champions will be without the services of suspended midfielder Akbar Imani on Wednesday at Sheik Jassim Bin Hamad Stadium.
Omid Ebrahimi's 12th minute strike had given Sepahan the lead at Foolad Shahr Stadium, although the home side were unable to build on the early opener as Imani was sent-off after picking up a second yellow card with over half an hour of the first leg remaining.