The talks mediated by Oman follow a massive US military build-up in the region not seen in decades, with President Donald Trump threatening to strike Iran if a deal is not reached.

"Our Supreme Leader has already stated that we will not have nuclear weapons at all," President Masoud Pezeshkian said, in a reference to Ayatollah Ali Khamenei.

While Iran has insisted the talks focus solely on its nuclear programme, the US wants Tehran's missile programme and its support for militant groups in the region curtailed.

The developments follow a massive protest movement that rights groups say saw thousands of demonstrators calling for the end of the Islamic republic killed.

In his State of the Union address on Tuesday, Trump accused Iran of "pursuing sinister nuclear ambitions", though Tehran has always insisted its programme is for civilian purposes.

Trump also claimed Tehran had "already developed missiles that can threaten Europe and our bases overseas, and they're working to build missiles that will soon reach the United States of America".

The Iranian foreign ministry called these claims "big lies".

The maximum range of Iran's missiles is 2,000 kilometres (1,200 miles) according to what Tehran has publicly disclosed.

However the US Congressional Research Service estimates they top out at about 3,000 kilometres -- less than a third of the distance to the continental United States.

Trump's State of the Union accusations in Congress were delivered in the same forum in which then-president George W. Bush laid out the case for the invasion of Iraq in 2003.

Ahead of Thursday's talks, Secretary of State Marco Rubio warned that Iran must also negotiate on its missile programme, calling Tehran's refusal to discuss ballistic weapons "a big, big problem".

He followed up by saying "the president wants diplomatic solutions".

But US Vice President JD Vance told Iran to take Trump's threats "seriously", saying the US president had a "right" to use military action.

"You can't let the craziest and worst regime in the world have nuclear weapons," Vance told "America's Newsroom" on Fox News.

On February 19, Trump said Iran had 15 days to make a deal.

- 'Expect a war' -

Foreign Minister Abbas Araghchi, who is leading the Iranian delegation at the talks, has called them "a historic opportunity", adding that a deal was "within reach".

In a foreign ministry statement that followed a meeting with his Oman counterpart, Araghchi said the success of the US negotiations depend "on the seriousness of the other side and its avoidance of contradictory behaviour and positions".

The US will be represented by envoy Steve Witkoff and Jared Kushner, who is married to Trump's daughter Ivanka.

The two countries held talks earlier this month in Oman, which is mediating the negotiations, then gathered for a second round in Geneva last week.

A previous attempt at negotiations collapsed when Israel launched surprise strikes on Iran last June, beginning a 12-day war that Washington briefly joined to bomb Iranian nuclear sites.

In January, Tehran launched a mass crackdown on nationwide protests that have posed one of the greatest challenges to the Islamic republic since its inception.

Trump threatened several times to intervene to "help" the Iranian people.

Emile Hokayem, senior fellow for Middle East security at the International Institute for Strategic Studies, said that "the region seems to expect a war".

"There's a lot of apprehension at this point, because the expectation is that this time" a war would be "bigger" than the one in June.

Tehran residents who spoke to AFP were divided as to whether there would be renewed conflict.

Homemaker Tayebeh noted that Trump had "said that war would be very bad for Iran".

"There would be famine and people would suffer a lot. People are suffering now, but at least with war, our fate might be clear," the 60-year-old said.

burs/ser/axn