Nuclear talks between Iran and world powers entered new territory Tuesday as negotiators embarked on what both sides predicted will be a long and difficult path towards a lasting deal.

The aimed-for historic accord would essentially let Iran retain its civilian nuclear programme, but on a modest scale and with enough oversight to make developing atomic weapons all but impossible.

Success could lead to Tehran and Washington normalising relations after a 35-year chill and could even bear fruit in other areas, such as Syria.

But failure might lead to conflict.

The scheduled three-day meeting in Vienna between Iran, the United States, China, Russia, Britain, France and Germany follows an interim deal struck in Geneva in November that they now want to transform into a permanent agreement.

Iran's supreme leader Ayatollah Ali Khamenei, who Tuesday took to Twitter to denounce nuclear weapons, set a cautious tone Monday when he said this effort would "go nowhere" but that he was not against trying.

"It is probably as likely that we won't get an agreement as it is that we will," said one senior US administration official.

"But these negotiations are the best chance we have ever had."

Iranian Foreign Minister Mohammad Javad Zarif was more upbeat, saying late Tuesday that a deal was "totally achievable" but needed "some innovation and some forward thinking".

On Tuesday the parties held two plenary sessions as well as several bilateral meetings, including a "productive" 80-minute one between the Iranian and US delegations, a senior US State Department official said.

A spokesman for the world powers' lead negotiator, EU foreign policy chief Catherine Ashton, said the aim of this Vienna round was a "workable framework to facilitate these negotiations".

Iran has long been suspected of seeking atomic weapons, despite its denials, and the US and Israel -- the latter assumed to have a large atomic arsenal itself -- have never ruled out military action.

- 'Band-aid solution' -

Under the November accord which took effect on January 20, Iran scaled back certain nuclear activities in exchange for minor sanctions relief and a promise of no new sanctions.

The freeze only lasts until July 20 -- although it can be extended -- and experts say that success in Geneva came at the price of postponing the really difficult issues.

"Geneva really was a stop gap, a band-aid solution that didn't really heal the wounds," Siavush Randjbar-Daemi, Iran and Middle East lecturer at Manchester University, told AFP.

Under the "comprehensive" solution that the parties aim to sew up by November, the six powers want Iran to scale back for a "long-term duration" its nuclear programme.

This might include closing the underground Fordo facility, slashing the number of uranium centrifuges, cutting the stockpile of fissile material, altering a new reactor being built at Arak and tougher UN inspections.

In exchange, all UN Security Council, US and EU sanctions on Iran -- which are costing it billions of dollars every week in lost oil revenues, wreaking havoc on the economy -- would be lifted.

But whether Iran will play along remains to be seen. Before the talks, Tehran had set out a number of "red lines", including a refusal to dismantle any facilities.

- Washington's watching -

Those in Vienna will be well aware that whatever they agree will need to be sold not only to other countries like Israel and the Sunni Gulf monarchies, but also back home.

US President Barack Obama has members of Congress breathing down his neck, threatening more sanctions and demanding -- with Israel -- a total dismantlement of Iran's nuclear facilities.

Zarif said that talk of new US sanctions had created "a great deal of concern in Iran on whether US is serious about wanting to reach an agreement".

Iranian President Hassan Rouhani, whose election in 2013 has helped thaw relations with the West, is on thin ice with hardliners seeking to turn Khamenei against him.

"The trouble is that both sides have hard men outside the negotiating room who have to be satisfied," Richard Dalton, the former British ambassador to Tehran now at think-tank Chatham House, told AFP.