Conflict has escalated in the past several days between US forces and Iranian-aligned militias in eastern Syria, which has been at the centre of the 12-year international struggle in the country.
The outcome will also affect Russia and Turkey ― which have troops there and are keen to expand their on interests ― and Damascus, amid Arab and Turkish efforts for a rapprochement with President Bashar Al Assad.
Washington has made it clear that treating Damascus like any normal government will embolden the regime, which it blames for the failure to implement UN resolutions on a political transition and the safe return of millions of refugees.
The US has also acted as the bulwark against a Turkish drive to take territory in northern and eastern Syria captured by a Kurdish militia known as the People's Protection Units, or YPG, which helped to defeat ISIS there four years ago.
On Thursday, a drone attack killed an American contractor at a US base in Hasakah governorate, which is largely under YPG control.
The killing drew US air strikes on Iranian-aligned militia in the nearby governorate of Deir Ezzor. More retaliations followed, although the violence lessened on Sunday.
"Mr Al Assad and Iran are seeing the Americans as their only remaining problem in Syria," said an officer who defected from the Syrian military and joined the opposition.
"Everyone else is seeking to reconnect with the regime."
Tension after Iran deal pull-out
Since the US pulled out of the Iran nuclear deal five years ago, there have been dozens of attacks on American bases in eastern Syria, which Washington has blamed on Iran-aligned militias.
But US retaliation this time has focused on urban targets in Deir Ezzor, inside the provincial capital and in the city of Mayadeen, as opposed to outlying areas of desert.
Areas south of the Euphrates river in Deir Ezzor are largely controlled by pro-Iranian militias, some of whom are also based in Iraq.
Areas north of the river are controlled by the Syrian Democratic Forces, a paramilitary force set up by the US and dominated by the YPG.
The Syrian officer said that Thursday's attacks on US bases, one of which killed the contractor, would have been difficult without the pro-Iranian militias obtaining Moscow's approval.
"Before Ukraine the Russians would have likely tried to warn the Americans of such an attack," he said, referring to the deterioration of ties between Moscow and Washington since the invasion of Ukraine.
He said Russian bases in Deir Ezzor city and in a desert area to the south monitor Iranian movements in the area, which is largely inhabited by Sunni tribes who changed allegiances during the 12-year conflict, having initially joined the revolt against five decades of Assad family rule.
The Syrian conflict started in 2011, when the regime suppressed mass pro-democracy demonstrations that started in southern Syria.
By the end of the year the revolt had militarised and Mr Al Assad lost large parts of the country to rebels supported by Arab and Western countries.
Shiite militias recruited by Iran helped the regime preserve its seat of power in Damascus and, in late 2015, intervention by Russia regained major cities and towns to the central government.
But Syria remains fragmented, with the US, Turkey, Russia and Iran each having spheres of influence manned by local or foreign militias.
Deir Ezzor, which borders Iraq, is regarded as a crucial link in a supply route between Iran and Hezbollah in Lebanon.
The route passes through Iraq, including the strategically important border town of Al Qaim, through to Abu Kamal on the Syrian side of the border in Deir Ezzor, and the governorate of Homs on the border with Lebanon, where Hezbollah has a significant presence.
In a letter to Congress, US President Joe Biden said that the American strike on Deir Ezzor were to “deter … Iran and Iran-backed militia groups from conducting or supporting further attacks on United States personnel".
A coalition of Shiite militias, mostly Iraqi, operate in eastern Syria, with some of their commanders having defected to Iran during the Iraq-Iran war between 1980 to 1988.
Among them is Kataib Hezbollah, the most well-armed non-state group in Iraq, the Imam Ali Brigades, Kataib Sayyed Al Shuhadaa and Hezbollah Al Nujabaa.
Most of them also have a presence on the Iraqi side of the border with Syria, to secure the supply line to Hezbollah in Lebanon.
An official working for the Kurdish-dominated administration in eastern Syria said although it was impossible to know for certain why Iran chose to initiate the confrontation, moves by Washington in recent months to strengthen the pro-US administration in eastern Syria may have been a factor.
He cited US efforts to solve differences between the YPG and Arab tribes, as well as putting pressure on the YPG to moderate its suppression of Kurds opposed to militia rule.
Turkish attacks on Kurdish targets in Syria over the past year, he said, also eliminated many Kurdish commanders with channels to Iran.
These commanders belonged to the Kurdistan Workers Party, a senior Turkish parent organisation to the YPG.
"Iran is sending a message that it is still a main power in the area," the official said.