The press conference will be held Thursday at the presidential office Cheong Wa Dae.
The president will first address the nation for about 20 minutes starting at 10 a.m. from his main office.
He will then move to a separate room where he will take questions from about 200 journalists from local and foreign news outlets for nearly 80 minutes.
Cheong Wa Dae earlier said the question-and-answer session will somewhat resemble a town hall meeting where the journalists may freely ask any questions they have.
North Korea will likely top the list of issues to be discussed as Moon and his government await a visit by North Korean leader Kim Jong-un to Seoul.
Kim's trip, if made, will mark the first of its kind by a North Korean leader at least since the end of the 1950-53 Korean War.
Inter-Korean relations quickly improved following three bilateral meetings between Moon and Kim last year, but the North has yet to completely give up its nuclear ambitions, also despite the first-ever U.S.-North Korea summit held in Singapore in June.
Kim is also set for his second summit with US President Donald Trump.
The economy is another major yet thorny issue for Moon as many believe Asia's fourth-largest economy is showing signs of a slowdown, partly due to Moon's ambitious plan to build what he calls an inclusive, welfare state.
The country's minimum hourly pay rate jumped nearly 30 percent in the less than two years since Moon took office in May 2017, while the government is also expanding its spending on social welfare, apparently placing an additional burden on local businesses.
President Moon may also face many questions regarding how he plans to run his government for the remainder of his single five-year term that will end in May 2022.
Moon was elected in a rare presidential by-election caused by the ouster of former leader Park Geun-hye over various corruption and power abuse charges that included illegal surveillance of civilians.
The Moon Jae-in administration currently faces the same allegation after one of its former inspectors from Cheong Wa Dae claimed to have spied on civilians at orders from his superiors.
Cheong Wa Dae has denied the accusation, noting the former inspector did in fact spy on civilians but made the decision to do so on his own, going against several warnings from his superiors.
It also says any illegal information or intelligence gathered by the former inspector was destroyed by his immediate superiors.
Thursday's news conference will be Moon's third press conference broadcast live on television. (Yonhap)