On Saturday, the Syrian military targeted at least one intruding Israeli F-16 warplane that had attacked an army base in central Syria, sending it down in flames and smoke.
The prime minister said that he has been warning for months about the dangers of Iran's military entrenchment in Syria.
"This is a serious Iranian attack on Israeli territory".
The Russian foreign ministry said it was seriously concerned by the latest developments in Syria and called for restraint.
In a statement today (Saturday), Lebanon's Foreign Ministry said it will complain to U.N. Security Council.
"You know that the great Leader of the Islamic Revolution, Imam Khamenei, has pronounced that the Zionist regime will end in less than 25 years and with the blessings of God, the Iranian nation will realize this truth", he maintained.
Israel has conducted dozens of strikes inside Syrian borders to defend what it calls its red lines, and to prevent what it says is Iran's proxy Hezbollah - fighting alongside the Syrian regime - from acquiring advanced weaponry.
In his conversation with Putin - with whom he met last week in Moscow - Netanyahu said he reiterated Israel's "right and obligation" to defend itself against attacks emanating from Syrian territory. "Whoever is responsible for this incident is the one who will pay the price".
Meanwhile, Ambassador to the UN Danny Danon called on the Security Council not to stand idle "when Iran acts to dangerously escalate the situation in the region", adding that the council must "condemn this risky step and immediately end the Iranian provocations". "To cover their crimes in the region, Israeli officials are resorting to lies against other countries", foreign ministry spokesman Bahram Ghasemi told AFP.
Separately, Iran issued a joint statement alongside the other main allies of the Syrian regime - Russian Federation and Lebanese militant group Hezbollah - denying the allegations regarding the drone.
Israeli military officials accused the Syrians and Iranians of "playing with fire", but indicated that Israel wanted to contain the situation.
"We consider it necessary to unconditionally respect the sovereignty and territorial integrity of Syria and other countries of the region", it added. The broadcaster said sounds of explosions were heard Saturday in Reef Damascus province, near the capital city.
An open conflict between Israel and Iranian-backed forces would add to the entanglements and chaos in Syria.
Iranian and Quds forces have been working for a while from the Syrian T4 air force base near Palmyra, Syria, supported by Syrian armed forces and with the approval of the Syrian government.
Four Iranian targets in Syria and eight Syrian ones belonging to the Fourth Syrian division near Damascus were attacked, according to the IDF.
Despite more Syrian anti-aircraft fire, all Israeli jets returned to base safely from the second mission, after the first jet was lost, according to the Israeli military.