In Vienna, the UN nuclear agency will once again urge Iran to stop stonewalling its inquiry into suspected atomic bomb research by Tehran, which denies any intent to make such arms.
The talks started around 10 A.M. (0800 GMT) at Iran's diplomatic mission in the Austrian capital.
"Differences remain but we ... are determined to solve these issues," Herman Nackaerts, deputy director general of the International Atomic Energy Agency (IAEA), told reporters.
Later over dinner in Istanbul, the European Union's top diplomat will meet Iran's chief nuclear negotiator - also now a presidential candidate - to discuss a broader diplomatic effort bid to resolve a row that could ignite war in the Middle East.
The two sets of talks represent distinct diplomatic tracks but are linked because both center on suspicions that Iran may be seeking the capability to assemble nuclear bombs behind the facade of a declared civilian atomic energy program.
Any movement in the decade-old standoff will probably have to wait until after Iranians vote on June 14 for a successor to President Mahmoud Ahmadinejad, analysts and diplomats say.
Even though it is Supreme Leader Ayatollah Ali Khamenei who decides Iran's nuclear policy, the conservative leadership may want to tread cautiously ahead of a poll in which loyalists will be challenged by two major independents.
With the election coming up, "the Iranians will do everything to keep everything stable," one Western envoy said.
Israel and the United States have threatened possible military action if diplomacy and increasingly tough trade and energy sanctions fail to make Iran curb its nuclear program.
Tehran says its nuclear activity has only peaceful purposes and that it is Israel, widely believed to be the Middle East's only nuclear-armed power, that threatens peace and stability in the region.
The IAEA has been trying for more than a year to coax Iran into letting it resume an inquiry into what the UN watchdog calls the "possible military dimensions" of its nuclear work.
Wednesday's talks in Vienna will be the 10th round of negotiations between the two sides since early 2012, so far without a framework agreement that would give the IAEA the access it wants to sites, officials and documents.
Iran's IAEA envoy, Ali Asghar Soltanieh, said this week he expected progress to be made in the discussions. But Western diplomats voiced pessimism.
The Istanbul meeting between EU foreign policy chief Catherine Ashton, who represents six world powers, and Iran's chief nuclear negotiator Saeed Jalili follows a failed round of big-power diplomacy in Kazakhstan in early April.
The gap is wide: the powers want Iran to suspend its most sensitive nuclear activity. Iran wants them to recognize its "right" to enrich uranium - which can have both civilian and military purposes - and to end tough economic sanctions.
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