Time is running out, with Kerry and Mohammad Javad Zarif aiming to agree the outlines of a potentially historic agreement by the end of the month. A full accord is then due by July 1.
Both men, meeting in a luxury hotel in the Swiss lakeside city of Lausanne, are also under intense pressure from domestic hardliners worried they will give too much away.
Speaking in Egypt over the weekend, Kerry sought to ease such concerns, saying that the aim is "not just to get any deal, it is to get the right deal".
There were, however, "important gaps," he said.
Zarif said yesterday that "several questions need to be discussed, those where we haven't found a solution yet and also those where we have found solutions but where we need to discuss certain details."
Kerry and Zarif met for nearly five hours today, together with Iran's nuclear chief Ali Akbar Salehi and US Energy Secretary Ernest Moniz and then alone.
The talks broke for Zarif to travel to Brussels to meet his British, French and German counterparts and the EU representative later today but he was due to return to Lausanne for more talks.
EU foreign policy chief Federica Mogherini said in Brussels before her meeting with Zarif that the talks were "entering a crucial time".
The United States and Iran have not had diplomatic relations for 35 years but the 2013 election of President Hassan Rouhani resulted in a minor thaw and a diplomatic push to resolve the more than decade-old nuclear standoff.
Under a landmark November 2013 interim deal with the "P5+1" powers, Tehran stopped expanding its activities in return for minor sanctions relief.
But to the alarm of Iran's foe Israel, US Republicans and Washington's Gulf allies, the US looks to have abandoned demands that Iran dismantle all nuclear activities.
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