Backed by Russian Federation and Iran, Assad has vowed to defeat the opposition fighters in Idlib if they do not surrender to Syrian government rule.
Turkey has been working with Iran and Russian Federation to find a peaceful solution to the Idlib crisis, warning that a full-scale operation on the province would result in a humanitarian disaster.
"We know that the Syrian armed forces are getting ready to solve this problem", President Vladimir Putin's spokesman Dmitry Peskov said on Tuesday, calling Idlib a "pocket of terrorism".
De Mistura told reporters that ongoing talks between Russian Federation and Turkey held the key to averting an assault on the region, but six reported air strikes on Tuesday suggested the Ankara talks were not going well. The Britain-based Syrian Observatory for Human Rights reported 9 people killed.
U.S. President Donald Trump warned Syria in a tweet Monday evening not to "recklessly attack" attack Idlib. "Don't let that happen!"
With some 3 million people now living in Idlib and the surrounding area, United Nations officials have warned that a government offensive could displace 800,000 people.
The presidents of Iran, Russia and Turkey are set to hold a meeting in Tehran on Friday to discuss the situation in Idlib.
Zarif said in Damascus that those talks also would focus on the battle against remaining militant groups that are fighting government forces in Syria.
Iranian Foreign Minister Mohammad Jawad Zarif said Tuesday that his country was making efforts to removed armed rebel forces from Idlib with as little "human cost" as possible.
The International Crisis Group, a Brussels-based think tank, said an all-out assault on Idlib and its catastrophic consequences could still be avoided.
Asked about Trump's tweet, Peskov said such warnings do not consider "the unsafe and negative potential" of the rebel-held enclave and show that the White House does not have a "comprehensive approach" to solving the Syria crisis. Restoration of Damascus's control of this province will put an end to large-scale military confrontation in Syria.
But analysts still say the United States appears resigned to the likelihood of a final military victory by Syrian government forces.