"Russia vows to shoot down any and all missiles fired at Syria," Trump said in a tweet. "Get ready Russia because they will be coming, nice and new and 'smart.'"
His comments follow an alleged chemical attack on a rebel enclave near Damascus over the weekend, and come after the Russian Ambassador to Lebanon, Alexander Zasypkin, warned that American military assets would be targeted in the event of a strike against Syria.
"If there is a strike by the Americans, then we refer to the statements of President [Vladimir] Putin and the chief of staff that the missiles will be downed and even the sources from which the missiles were fired," he told Hezbollah's al-Manar TV.
The Russian military announced later on Wednesday that it was sending troops to secure Douma, where dozens were allegedly killed Saturday in a suspected poison gas attack.
A Russian Foreign Ministry spokeswoman, Maria Zakharova, also told NBC News that "there are Russians present in large numbers in Syria, and Russia will do everything to protect its people on Syrian soil."
Zakharova responded to Trump's comments in a subsequent Facebook post.
"Smart missiles should be aimed at terrorists, not at the legitimate [Syrian] government that is fighting international terrorism on its territory," she said.
Zakharova asked whether the U.S. was trying to sabotage an investigation into the suspected poison gas attack.
"Is that the actual plan — to cover up all evidence of this fabricated attack with smart missile strikes, so that international inspectors have no evidence to look for?" she added.
The U.S. has heaped condemnation on Syria and its main backer Russia since images emerged of the aftermath of the possible chemical attack in the rebel-held enclave.
Trump canceled a trip to Latin America to focus on the Syria incident, the White House said. He told reporters all options were on the table regarding Syria, a sentiment Press Secretary Sarah Huckabee Sanders echoed Wednesday.
She defended the president's threats toward Russia, saying that he isn't telegraphing any military action by tweeting his thoughts. She said Trump is withholding any particular timetable on military action and "missiles" represent just one of many options he is considering, and no final decisions have been made.
Defense Secretary Jim Mattis, who also canceled plans to travel to California in the coming days, sounded a more cautious note.
"We are still assessing the intelligence — ourselves and our allies," he told reporters alongside his Dutch counterpart Wednesday. "We're still working on this."
The USS Donald Cook, a Navy destroyer, left a port in Larnaca, Cyprus on Monday. The guided-missile destroyer is armed with Tomahawk cruise missiles, which were used a year ago after an alleged sarin gas attack on Syrian civilians.
French President Emmanuel Macron has called for a "strong and joint response" to the latest incident.
Macron also said France, the U.S. and Britain would decide how to respond in the coming days.
"Chemical weapons capabilities" were legitimate targets, he said, but added that allies of Syrian President Bashar al-Assad were not. In addition to Russia, Iran and Iran-backed Lebanese group Hezbollah support the Syrian strongman.
Trump has also spoken by phone with British Prime Minister Theresa May, who on Wednesday said all indications were that the Syrian government was behind the attack in Douma.
"The use of chemical weapons cannot go unchallenged," she told reporters in Birmingham, central England. "We'll be working with our closest allies to consider how we can ensure that those responsible are held to account, and also how we can prevent and deter the humanitarian catastrophe of the use of chemical weapons in the future."
Eurocontrol, the pan-European air traffic control agency, warned airlines Tuesday to exercise caution in the eastern Mediterranean due to possible airstrikes in the next 72 hours. Air France confirmed to NBC News that it had heeded the warning and adjusted its plans for its Beirut and Tel Aviv flights.
"The company's security division is closely monitoring developments," a spokesperson added.
Retired Adm. James Stavridis, a former head of NATO and an NBC News analyst, warned that any U.S. strike on Syria would likely require manned aircraft and characterized it as a "high-risk operation."
"Last year was about sending a signal," Stavridis said, referring to the April 2017 strike ordered by Trump. "This year its about destroying actual Syrian capability."
Retired Lebanese Gen. Khalil Helou said the ultimate objective of any U.S. action should be to force Assad to change course.
"The aim is to soften the rigidity of Assad, to push him to accept, at least, starting of a peace process in Syria," he said.
On Wednesday, the World Health Organization said it was "deeply alarmed by the reports of the suspected use of toxic chemical" in Douma.
"More than 70 people sheltering in basements have reportedly died, with 43 of those deaths related to symptoms consistent with exposure to highly toxic chemicals," it said in statement.
Around 500 patients were seen at local hospitals and clinics and showed symptoms consistent with exposure to toxic chemicals, it said.
"We should all be outraged at these horrific reports and images from Douma," said Dr. Peter Salama, WHO's director general.
The Russian Defense Military labelled the WHO statement "unfounded," and called reports of an attack a "fabrication and provocation."
Some 500,000 people are estimated to have died in the Syrian civil war as Assad fights rebels trying to unseat him. Millions of Syrians have been forced from their homes.
F. Brinley Bruton reported from London, Keir Simmons from Moscow, and Bill Neely and Charlene Gubash from Beirut, Lebanon.