The talks paused in June on a positive note, with diplomats saying they were "close" to an agreement, but the arrival of ultraconservative Iranian President Ebrahim Raisi in office has changed the outlook.
Iran ignored appeals from Western countries to restart the talks for several months, all the while strengthening the capabilities of its nuclear programme.
While the talks are now finally restarting, the mood music is downbeat.
The US Special Envoy for Iran Rob Malley has said that Tehran's attitude "doesn't augur well for the talks".
"If they start getting too close, too close for comfort, then of course we will not be prepared to sit idly," Malley told the US National Public Radio earlier this week.
The 2015 deal, also known as the Joint Comprehensive Plan of Action (JCPOA), offered a lifting of some of the array of economic sanctions Iran had been under in return for strict curbs on its nuclear programme.
But the deal began falling apart in 2018 when then US president Donald Trump pulled out and began reinstating sanctions on Iran.
The following year, Iran retaliated by starting to exceed the limits on its nuclear activity laid down in the deal.
In recent months, it has started enriching uranium to unprecedented levels and has also restricted the activities of inspectors from the International Atomic Energy Agency (IAEA), the UN watchdog charged with monitoring Iran's nuclear facilities.
IAEA Director General Rafael Grossi visited Tehran last week in the hope of addressing several bones of contention between the agency and Iran.
However, he said on his return that "no progress" had been made on the issues he raised.
In order not to jeopardise the JCPOA talks, Western diplomats decided not to press for a resolution critical of Iran at last week's meeting of the IAEA's Board of Governors.
However, the US has said it could convene a special meeting of the board in December if the impasse continues.
"Iran's unwillingness to reach a relatively straightforward compromise with the IAEA reflects poorly on the outlook for the nuclear talks," according to Henry Rome, Iran specialist at the Eurasia Group.
"Iran may calculate that its unconstrained nuclear advances... will put more pressure on the West to give ground in talks quickly," Rome said in a note, but added that this would instead "likely have the opposite effect".
"The situation regarding Iran's nuclear advances is increasingly precarious," Kelsey Davenport, an expert with the Arms Control Association, told journalists in a briefing last week.
"While the Trump administration manufactured this crisis, Iran's actions are really prolonging it," Davenport said.
"Iran is acting like the United States is going to blink first but... pressure is a double-edged sword" which could kill any prospect of the 2015 deal being restored, she added.
One particular area of concern for the IAEA is a centrifuge components manufacturing unit in Karaj, near Tehran.
The IAEA has not had access to the site since its cameras there were damaged by an "act of sabotage" in June.
Iran has accused arch-foe Israel of carrying out an attack on the site.
"If there are gaps in the IAEA's monitoring, it will drive the speculation that Iran has engaged in illicit activity, that it has a covert programme, whether there's evidence to that or not," Davenport pointed out, which could in turn "undermine the prospects for sustaining the deal".
The talks will take place in the Palais Coburg hotel where the 2015 agreement was clinched.
Along with Iran, diplomats from the UK, China, Germany, Russia and France will attend.
The US will take part in the talks indirectly.
Top Israel diplomat Yair Lapid was meanwhile scheduled to meet Monday with British Prime Minister Boris Johnson and Foreign Secretary Liz Truss in London, and with French President Emmanuel Macron in Paris on Tuesday.
Former Israeli prime minister Benjamin Netanyahu was among the most vocal critics of the 2015 deal.
Russia's ambassador to the UN in Vienna Mikhail Ulyanov noted on Saturday that the talks had been subjected to "a very protracted pause".
"There is the obvious need to speed up the process," Ulyanov said.
The US has already warned it will turn to "other efforts... to address Iran's nuclear ambitions" if the talks fail but analysts say there are no obvious options available outside the negotiations.