The negotiations formally got under way in the Kazakh city of Almaty - which follows three inconclusive meetings last year in Istanbul, Baghdad and Moscow - at around 1:30 p.m (0730 GMT).
But with the Islamic Republic`s political elite pre-occupied with worsening internal infighting ahead of a June presidential election, few believe the meeting Tuesday and Wednesday in the Kazakh city of Almaty will yield an immediate breakthrough.
At best, diplomats and analysts say, Iran will take the joint offer from the United States, Russia, France, Germany, Britain and China seriously and agree to hold further talks soon on how to implement practical steps to ease the tension.
The powers would like to see "a recognition by our Iranian colleagues that our offer is a serious one ... but it is not the final act in the play," said one diplomat participating in the talks. "I wouldn`t predict a decisive breakthrough."
Iran is showing no sign, however, of backing down over a nuclear program it says is for entirely peaceful energy purposes. The program has drawn tough Western sanctions that have greatly reduced its oil exports, an economic lifeline.
A U.N. nuclear watchdog report last week said Iran was for the first time installing advanced centrifuges that would allow it to significantly speed up its enrichment of uranium, which can have both civilian and military purposes.
Tightening Western sanctions on Iran over the last 14 months are hurting Iran`s economy, slashing oil revenue and driving the currency down, which in turn has pushed up inflation.
But they are not close to having the crippling effect envisaged by Washington, analysts say, and - so far at least - have not prompted a change in nuclear course by Tehran.
Western officials say the powers` offer - an updated version of one rejected by Iran in the last meeting in June - would include an easing of sanctions of trade in gold and other precious metals if Tehran closes its underground Fordow enrichment plant.
The stakes are high. Israel, assumed to be the only nuclear-armed power in the Middle East, has hinted strongly at possible military action to prevent its foe from obtaining such arms. Iran has threatened to retaliate hard if attacked.
The fact that the meeting takes place in Kazakhstan - which gave up its nuclear arsenal after the collapse of the Soviet Union in the early 1990s - has symbolic resonance.
A U.S. official said the Central Asian state could serve as a "good role model" for the benefits of making "certain choices", in clear reference to Iran`s atomic ambitions.
Western officials acknowledge an easing of U.S. and European sanctions on trade in gold represents a relatively modest step. But it could be used as part of barter transactions that might allow Iran to circumvent tight financial sanctions.
Iran so far appears to be showing little interest. Its Foreign Ministry spokesman last week dismissed the reported incentive as insufficient and a senior Iranian lawmaker has ruled out closing Fordow, located close to the holy city of Qom.
Iran says it enriches uranium to a fissile concentration of 20 percent to make fuel for a medical research reactor in the capital Tehran. But it also represents most of the work required to reach weapons-grade material of 90 percent.
A U.S. official said the powers hoped that the Almaty meeting would lead to follow-up talks, either at a political or technical level, before Iran`s New Year celebrations in March.