The opposition Democratic Party (DP), which already dominates the 300-member legislature, has hammered Yoon and his conservative People Power Party (PPP) for mismanaging the economy and failing to rein in inflation.
PPP leader Han Dong-hoon said a big win by the DP, whose leader is facing corruption charges, would create a crisis for the country. He warned against giving the opposition an unprecedented super majority of 200 seats.
Opinion polls are mixed and the two major parties have said dozens of districts are too close to call but some party leaders and political analysts predict DP is likely to win a majority.
Yoon, about to enter the third year of his five-year presidential term, has been suffering from low approval ratings for months, having come to power in 2022 vowing to cut taxes, ease business regulations and expand family support in the world's fastest ageing society.
Kookmin University political science professor Hong Sung-gul said this election will be a retrospective on Yoon's performance rather than a choice about future policy issues, as well as a measure of how divided society has become politically.
"A major factor here is the judgment that President Yoon Suk Yeol has not been good at making the right decisions politically, and there's discontent about that," he said.
Democratic Party leader Lee Jae-myung said his team needs a clear majority to deliver the message of judgment against Yoon's failed government and is cautiously confident that it can significantly increase its dominance.
A liberal splinter party led by former justice minister Cho Kuk has emerged a dark horse, projected to win a dozen seats to become a third-party force that can influence control of the assembly.
Corruption has been a major campaign issue.
Opposition leaders Lee and Cho are both on trial for fraud. First lady Kim Keon Hee has been accused of breaking the law by accepting a Dior bag as gift, while South Korea's ambassador to Australia resigned following questions about his appointment while he was under a corruption probe.
More than 30% of eligible voters have cast their ballots in two days of early voting last week in a record turnout. Polling stations open at 6 a.m. (2100 GMT Tuesday) and close at 6 p.m. (0900 GMT).
While Yoon has made it a top priority to strengthen security alliance with the United States and Japan, foreign policy has not played significantly on campaign trails and little change is expected on the diplomatic front whatever the result.
