"We will not allow Iran to establish a military presence in Syria," Benjamin Netanyahu told reporters, along with US envoy Brian Hook, who is visiting Israel.
Both Netanyahu and Hook called for an extension of the arms embargo on Iran, the archenemy of their countries, which expires in October.
"I say to Ayatollah in Tehran ... Israel will continue to take the necessary measures to prevent you from creating a terrorist front and another military front against Israel" in neighboring Syria, he added. "I say to Bashar al-Assad: You risk the future of your country and your regime."
Israel has launched hundreds of strikes in Syria since its civil war began in 2011, targeting government and allied Iranian forces and Lebanese Shiite Hezbollah guerrillas.
Netanyahu said, "We are absolutely determined to prevent Iran from establishing itself militarily in our immediate surroundings."
Hook also focused on the arms embargo, which was developed as part of a multilateral nuclear agreement signed by Tehran, Washington, and other major powers in 2015.
The US envoy said that lifting this ban would allow Iran to "import combat aircraft, attack helicopters, warships, submarines, advanced artillery systems and missiles."
"Iran will then be in a position to export these weapons and technologies to their proxies such as Hezbollah, Palestinian groups such as Islamic Jihad and Hamas, Shiite militias in Iraq, Shiite militant networks in Bahrain and the Houthis in Yemen," Hook added.