The talks, led by Steve Witkoff and Abbas Araqchi, mark an effort to turn the interim 14-point pact into a lasting regional deal to end the war that the US and Israel launched on February 28.
But just hours after a ceasefire took effect in Lebanon between Israel and Iran-backed militants Hezbollah, Israeli air strikes and drone attacks killed at least five people in the south on Saturday, Lebanese state media said.
A halt to the fighting in Lebanon is a condition for starting 60 days of US-Iranian talks to resolve disputes over Iran's nuclear program and other thorny issues needed to forge a more durable deal critical to reopening the Strait of Hormuz and stabilising global oil supplies.
The ceasefire in Lebanon took effect on Friday afternoon after an exchange of fire.
But Israeli warplanes and drones launched strikes across the Nabatieh area overnight and into Saturday morning, destroying residential buildings, while Israeli artillery shelled Nabatieh and its outskirts before dawn, Lebanese state news agency NNA said.
Witkoff was heading to Switzerland to join Jared Kushner, Trump's son-in-law, who was already there, while Araqchi would travel there on Saturday, Axios reported.
The White House did not respond to questions about Witkoff's travel, and Iran has not confirmed Araqchi's plans.
Vice-President JD Vance cancelled plans on Thursday to travel to the Swiss mountaintop resort of Buergenstock as preparations for technical talks were well advanced, amid rising tension between Israel and Hezbollah.
Wednesday's interim deal requires the US, Iran and their allies to declare an immediate and permanent termination of military operations on all fronts, including in Lebanon.
Israel, left out of the talks, says it is not party to the deal.
Araqchi, in a telephone call with his Pakistani counterpart on Friday, said the US would be responsible for any violation of its commitments under the deal, including ending the fighting in Lebanon, his ministry said.
Lebanon was sucked into the regional war when Hezbollah opened fire at Israel on March 2, prompting it to launch an offensive against the group and invade the south of the country.
Before Saturday's attacks, US Secretary of State Marco Rubio and Lebanese President Joseph Aoun discussed holding Israel-Lebanon negotiations in Washington from Tuesday to Thursday, the State Department said.
The Lebanese presidency said a comprehensive ceasefire was a fundamental pillar of these talks.
The Iran war has killed at least 7000 people, mostly in Iran and Lebanon, and has pushed up energy prices, stoking inflation worldwide.
Crude prices have fallen as oil shipments picked up through the Strait of Hormuz - a key conduit for global energy supplies - after the signing of the interim deal.
The body Iran set up to manage the strait said it would waive planned fees during the interim deal's negotiation period.
The interim deal foresees relief for Iran from economic sanctions, the unfreezing of assets worth tens of billions of dollars and immediate US waivers for its exports of oil.
It also provides for a $US300 billion ($A428 billion) reconstruction fund for Iran and other financial incentives.
Trump again defended the deal after criticism in Washington, including some from Republican allies who question whether he conceded too much to end an unpopular war ahead of midterm elections in November.
"The War has diminished Iran!" Trump wrote on social media on Friday, adding, "We didn't meet out of desperation, Iran did. They are FINISHED! We'll play out the 60 days. They get no money, not 10 cents!"
