The UN's Syria envoy called on the war-torn nation's rival sides to meet their historic responsibility and seek a deal to end the six-year conflict ahead of a full day of talks set for Friday.
The negotiations at the United Nations in Geneva formally opened Thursday with envoy Staffan de Mistura dampening hopes of a breakthrough.
"I'm not expecting miracles," he said at a welcoming ceremony while warning of dire consequences if the talks "fail again".
"This is... our solemn responsibility... a historical responsibility not to condemn the future generations of Syrian children to long years of bitter and bloody conflict," he said.
Syrian President Bashar al-Assad's negotiators are meeting the opposition for a fourth round of UN-brokered talks, clouded by persistent violence and deadlock over the country's political future.
De Mistura said he would hold bilateral meetings on Friday devoted largely to procedure.
The main opposition High Negotiations Committee (HNC) has said it wants to meet the government face-to-face.
Two other opposition groups based in Moscow and Cairo, who are also in the Swiss city, also want a seat at the table but the HNC has insisted it should remain the only rebel delegation.
De Mistura said his "dream" was to have one opposition grouping but noted that key divisions persist, especially over Assad's fate.
"It's still not very clear. Many questions remain up in the air. We still don't know if it will be direct negotiations. And we still don't know what will happen with the Cairo and Moscow groups," a western diplomat told AFP.
The HNC has demanded Assad leave office as part of any deal, while the Moscow and Cairo groups have a more moderate stance on the Syrian leader.
"There is still work to be done" in fostering unity among the various opposition factions, he told reporters.
The ground -- both in territory and diplomatically -- has shifted since the last UN-sponsored talks to end the conflict that has claimed more than 310,000 lives.
The rebels are now in a significantly weaker position.
The army has recaptured the rebel bastion of eastern Aleppo and the United States, once staunchly opposed to Assad, has said it is reassessing every aspect of its Syria policy under President Donald Trump.
Experts have said the rebels have lost much of their leverage giving the government little reason to compromise.
While acknowledging the major obstacles, de Mistura asked the sides to "work together."
"The Syrian people desperately want an end to this conflict and you all know it... they are awaiting for a relief from... suffering and dream of a new road out of this nightmare," he added.