Russian Foreign Minister Sergei Lavrov has said the rival Syrian delegations have agreed to sit down for direct talks on Friday.
He said that they should start with confidence-building measures at the peace conference in Switzerland, dubbed Geneva II.
Mr Lavrov, who said he held talks with Syrian Foreign Minister Walid al-Moualem and Syrian opposition leader Ahmed Jarba, urged the opposition and its foreign backers not to focus exclusively on leadership change in Damascus.
At the talks, Mr Jarba demanded the Syrian government delegation sign up to an international plan for handing overpower.
Mr Moualem insisted President Bashar al-Assad would not bow to outside demands.
"As for guarantees that the talks will not collapse - it is necessary to influence both delegations so that this does not happen," Mr Lavrov said.
"The main thing is to start the process," he said, adding their talks were expected to take about a week before a pause and a second round.
Mr Lavrov said the United Nations, Moscow and Washington were seeking to agree on a prisoner swap in Syria and exchanging lists of people it could potentially include.
He signalled progress in talks over a possible ceasefire in the northern city of Aleppo, after a Syrian government proposal in Moscow, and said similar discussions were going on about the central city of Homs, but gave no details.
"The relatively less difficult issues are confidence-building measures, humanitarian aid, prisoner swaps and, through this, some sort of relations between the two delegations should be created," he said.
Mr Lavrov said the so-called Geneva II conference in Montreux went as expected and hailed as a breakthrough the first time the Syrian government and opposition delegations sat at one table ahead of first direct talks in nearly three years of conflict.
Speaking to journalists before he left Switzerland for Moscow, Mr Lavrov said Russia would go on seeking to engage Iran in international talks on Syria and that domestic opposition groups- including Kurdish groups and the National Coordination Committee - should also take part.
Earlier, UN Secretary General Ban Ki-moon said the Syrian parties "can make a new beginning".
He told representatives of Syria's opposing sides and of those of around 40 nations that this "conference is your opportunity to show unity".
Calling the challenges ahead great but not insurmountable, he called for immediate access for aid to areas under siege.
United Nations mediator Lakhdar Brahimi said he hoped that detailed discussions, which begin in Geneva on Friday, will lead to a settlement.
A day of formal speeches under UN auspices at a hotel on Lake Geneva has raised no great expectations, particularly among Islamist rebels on Syria's frontlines.
Underlining the seemingly intractable positions, Mr Moualem said yesterday that Mr Assad's position was non-negotiable.
"The subject of the president and the regime is a red line for us and the Syrian people and will not be touched," he was quoted as saying in Syrian media.
He told delegates today that Syria will do what it takes to defend itself in ways that it deems appropriate.
He also called on the international community to stop pouring arms into Syria and supporting terrorism and urged the lifting of sanctions.
Mr Moualem also warned that the conflict "will not stop in Syria", but will affect all neighbouring countries.
Mr Lavrov, co-sponsor of the conference with Mr Kerry, repeated Moscow's opposition to "outside players" meddling in Syria's affairs but he also said Iran - Mr Assad's main foreign backer -should have a say.
Mr Kerry, in his brief speech to the floor, said negotiations would be "tough and complicated" but insisted there was "no way" Mr Assad could stay on with a transitional government.
"One man can no longer hold an entire nation or region hostage," Mr Kerry said, while also adding there would be no room in government for "terrorists" among the rebel forces.
A flap over a now withdrawn last-minute invitation to Iran also highlighted tensions between the West and Russia and the sectarian rift in the Middle East between Sunni Arabs who support the rebels and the Shia rulers in Tehran.
Iranian president Hassan Rouhani said the talks are unlikely to be successful.
"Because of the lack of influential players in the meeting, I doubt about the Geneva II meeting's success in fighting against terrorism ... and its ability to resolve the Syria crisis," Mr Rouhani said.
"The Geneva II meeting has already failed without it even being started."
The release on the eve of the talks of thousands of photographs apparently showing prisoners tortured and killed by the Syrian government reinforced opposition demands that Mr Assad must quit and face a war crimes trial.
The president, who succeeded his father 14 years ago, insists he can win re-election and wants to talk about fighting "terrorism".
Mr Assad has been protected by Russia, his main arms supplier, which dislikes Western attempts to overthrow incumbent leaders.
But Washington and Moscow share alarm at the spread of the violence that has already killed more than 130,000 Syrians.
Presidents Vladimir Putin and Barack Obama had a "businesslike" conversation on the issue by phone yesterday.
UN diplomats believe the talks could initially bring at least some relief for Syrian civilians, by improving aid flows, as well as setting up prisoner exchanges.