What is new this week is not simply another round of nuclear diplomacy, but the intensity of the regional effort behind it.
Officials say the priority of the Istanbul meeting is to prevent conflict, with countries including Saudi Arabia, Qatar, Egypt, Oman, Pakistan and the UAE invited at foreign-minister level as part of a broader attempt to start dialogue before tensions spiral.
The meeting is expected to bring US special envoy Steve Witkoff and Iran’s Foreign Minister Abbas Araghchi together, with regional mediators hoping the presence of Arab and Turkish ministers can help bridge gaps that have widened since talks collapsed last summer after Israeli and US strikes on Iranian nuclear facilities.
One regional official, speaking on condition of anonymity, said that US President Donald Trump’s son-in-law Jared Kushner will also attend alongside Witkoff if the meeting goes ahead.
According to Qatar's Foreign Ministry spokesperson, Majed Al-Ansari, on Tuesday, there is regional collaboration and ongoing efforts aimed at ensuring the de-escalation.
The UAE president's adviser Anwar Gargash told a panel at the World Governments Summit in Dubai on Tuesday, "I think that the region has gone through various calamitous confrontations. I don't think we need another one, but I would like to see direct Iranian-American negotiations leading to understandings so that we don't have these issues every other day."
Public rhetoric on both sides remains extreme, making it harder to judge where compromise lies.
Trump warned this week that with big US warships heading to Iran, "bad things" would likely happen without an agreement, while Iran’s leadership continues to insist it will not negotiate under threats.
Iranian President Masoud Pezeshkian said on Tuesday that he had instructed foreign minister to prepare the ground for talks with the United States.
“Given requests from friendly governments in the region for a response to the US president’s proposal for talks, I instructed the foreign minister to, if conditions are suitable – free of threats and unrealistic expectations – create the groundwork for fair and equitable negotiations, guided by the principle of dignity, wisdom, and expediency, within the framework of the national interest,” Pezeshkian said.
The existence of an Istanbul channel – and the involvement of multiple regional capitals – suggests both sides are still testing whether a deal is possible.
Where talks could bog down
The central diplomatic battle is over scope. Regional officials involved in the effort say mediators are trying to limit the talks to Iran’s nuclear program as the most realistic path to getting Tehran to “yes,” with one official describing the strategy as addressing Washington’s non-nuclear demands only later through innovative ways.
“If the talks happen, they will stay focused on Iran’s nuclear program. And then we will try to find innovative ways to address Washington’s nonnuclear demands,” the Washington Post cited a US official as saying.
The Trump administration, however, has been explicit that it wants more than nuclear limits – including constraints on Iran’s missile development and its support for allied militia groups across Iraq, Lebanon, Yemen and elsewhere.
That mismatch is likely to define the talks: Iran wants the file narrow, Washington wants it comprehensive.
Uranium stockpile and enrichment: the urgent nuclear core
At the heart of the talks is Iran’s uranium stockpile and enrichment capability.
The Trump administration has demanded that Tehran remove or transfer 400 kilograms (more than 900 pounds) of uranium enriched to 60% purity and curb enrichment activity it says is edging toward weapons capability.
Iran denies it intends to weaponize its program, but the question of what happens to existing stockpiles – whether moved abroad, frozen, or placed under tighter monitoring – remains one of the most immediate pressure points.
Analysts say one possible compromise could be suspending further enrichment without Iran explicitly renouncing what it claims as a right to enrich under the Non-Proliferation Treaty.
Missile program: Tehran’s red line
Iran has consistently signaled that its missile program is not up for negotiation.
That creates an early ceiling on what can be achieved if Washington insists on missile curbs as part of any package, reinforcing the mediator strategy of keeping the first phase focused tightly on the nuclear file.
Regional militias: the hardest unresolved layer
The US has also demanded that Iran reduce support for allied non-state groups across the region.
Iran is unlikely to publicly abandon those relationships, but experts suggest the sides could explore narrower understandings – such as a nonaggression framework that extends to both countries’ respective partners – rather than an explicit proxy rollback.
This is where the talks could either expand into a broader security negotiation or fracture under maximalist expectations.
What happens next
Officials caution that details of the Istanbul format remain unclear, but the “main meeting” is expected on Friday.
The immediate goal may be modest: establish a channel, prevent escalation, and see whether nuclear-focused diplomacy can restart – with missiles and regional militias left as the more difficult second-stage questions.
In that sense, Istanbul seems less about a final agreement than about whether the sides can still find a negotiating floor before confrontation becomes the default.
According to an Iranian diplomatic source cited by Reuters on Tuesday, Iran is "neither optimistic nor pessimistic" over the talks.