Five previous rounds of UN-backed negotiations have failed to yield a solution to the six-year conflict.
UN envoy Staffan de Mistura met twice on Tuesday with both the Syrian government delegation and the opposition High Negotiations Committee (HNC), with meetings at the UN headquarters running late into the evening.
De Mistura also met with deputy Russian foreign minister Gennady Gatilov earlier in the day, Moscow's foreign ministry said. Syrian state news agency SANA said Gatilov sat down with lead government negotiator Bashar al-Jaafari as well.
But hopes for a breakthrough remain dim, with tensions raised further by US claims of new regime atrocities at the notorious Saydnaya prison near Damascus.
The US State Department on Monday accused Bashar al-Assad's government of using a crematorium to cover up the deaths of thousands of prisoners at Saydnaya -- a claim Damascus swiftly denied.
"These allegations are totally unfounded, they are nothing but the product of the imagination of this administration and its agents," SANA quoted the foreign ministry as saying.
HNC spokesman Salem al-Meslet, speaking to AFP ahead of his delegation's first meeting, said the fresh accusations demanded a response.
"The Americans know what's going on in Syria now... To save the lives of Syrian people it needs some action from the (United) States, from our friends, and I hope they will do it very soon," he said.
- 'Working in tandem' -
The negotiations set to run to the weekend are the latest effort to end a war that has killed more than 320,000 people and displaced millions.
They are expected to focus on four separate "baskets": governance, a new constitution, elections and combating "terrorism" in the war-ravaged country.
But one issue -- Assad's fate -- remains a daunting roadblock.
The HNC has insisted the president's ouster must be part of any political transition, a demand unacceptable to the Syrian regime.
The HNC's first session with de Mistura focused on releasing detainees and a new constitution, Meslet told AFP after the meeting.
The Geneva talks have been overshadowed by a string of rebel evacuations from the Syrian capital and rival negotiations in the Kazakh capital, Astana.
Sponsored by rebel supporter Turkey and regime backers Russia and Iran, that track produced a May 4 deal to create four "de-escalation" zones across some of Syria's bloodiest battlegrounds.
De Mistura has dismissed suggestions that the Astana negotiations were competing with the Geneva track, saying they were "working in tandem."
The HNC insisted that UN-backed talks are by far the most critical.
"We only believe in deals that are agreed upon here in Geneva -- not in Astana," Meslet said.
- Russia 'must act' -
Assad, however, has given more credit to Astana and has blasted the Geneva process as "merely a meeting for the media."
The talks have also been impacted by the shifting role of the US, an erstwhile opposition supporter that largely withdrew from the process under President Donald Trump.
De Mistura said Monday he was "encouraged by the increasing engagement, the increasing interest" by Trump's administration.
Washington appeared to turn up the heat on Monday, warning Russia not to turn a blind eye to Assad's alleged crimes at Saydnaya.
"The United States is on record, has stated many times, that we are appalled by the atrocities that have been carried out by the Syrian regime," said Stuart Jones, the top US diplomat for the Middle East.
"Russia must now, with great urgency, exercise its influence over the Syrian regime to guarantee that horrific violations stop now."
One newly released image, a commercial satellite photograph dating back to January 2015, shows snow melting on the roof of a building attached to the Saydnaya military complex north of Damascus.
This, along with an earlier picture allegedly showing heavy-duty ventilation systems on the structure, appears to support earlier claims by rights groups that Saydnaya is an execution centre.
Geneva, Switzerland | AFP