Iran's newly elected President Hasan Rouhani is opting not to meet with Obama.
Officials are calling such a meeting too complicated despite a historic change in tone with Rouhani vowing not to build nuclear weapons.
"Iran poses absolutely no threat to the world or the region," Rouhani said.
Obama is sharing cautious optimism about moving forward to ease long-standing tensions with Iran.
"I do believe that if we can resolve the issue of Iran's nuclear program that can serve as a major step down a long road towards a different relationship" Obama said.
Obama addressed the General Assembly Tuesday morning. He's pressuring the U.N. Security Council to mandate consequences if Syria doesn't follow through with a plan to hand over its chemical weapons.
"Even when America's core interests are not directly threatened, we stand ready to do our part to prevent mass atrocities and protect basic human rights, but we cannot and should not bear that burden alone," Obama said.
The president is calling on world leaders to take risks in order to ease tensions in the Middle East, focusing on the conflict between Israel and Palestine, meeting with Palestinian President Mahmoud Abbas and again advocating a two-state solution.
"The time is now ripe for the entire international community to get behind the pursuit of peace," Obama said.
Obama returns to Washington Tuesday night and is now directing Secretary of State John Kerry to pursue a nuclear agreement with Iran. Kerry is scheduled to meet with Iran's foreign minister on Thursday.
Iran president ready for nuclear negotiations
Iranian President Hassan Rouhani says his nation is prepared to immediately engage in stalled negotiations over its disputed nuclear program - but only under certain conditions.
Rouhani told the United Nations General Assembly in New York on Tuesday that he is also open to talks with the United States "to manage differences." It was his first appearance on the world stage since he was elected in the summer.
Nuclear negotiations between Iran and six world powers have been stalled for months but Iran agreed to a new meeting this Thursday on the sidelines of the General Assembly.
Rouhani said every issue can be resolved through moderation and rejection of violence.
The Associated Press contributed to this story.
