Obama set a goal of ensuring all nuclear materials worldwide are secured from theft or diversion within four years.
The White House will seek concrete commitments from world leaders on securing stockpiles of separated plutonium and uranium, to ensure that they cannot be stolen, smuggled or sold.
"I feel very good at this stage in the degree of commitment and sense of urgency that I've seen from the world leaders so far on this issue," Obama said.
"We think we can make enormous progress on this."
The summit will focus primarily on separated plutonium and highly enriched uranium stocks, rather than radiological "dirty" bombs, which the US sees as a less catastrophic threat than nuclear devices.
Meir Javedanfar, a nuclear analyst, said the summit would also seek to form a coalition among the countries participating so they can "co-operate ... and then take another step further by going to the United Nations."
"I think al-Qaeda could get its hands on nuclear weapons if these checks and balances are not put in place to make sure that nuclear stockpiles around the world are kept in safe places," he told Al Jazeera from Tel Aviv.
US officials hope nations participating in the summit will agree on a series of security steps for their own nuclear material, and help pay to put the stocks of less well-off countries under lock and key.
They also expect some leaders to unveil specific actions, similar to Chile's decision to ship a stock of highly enriched uranium to the US.
Iran and North Korea were not invited to the conference.
The US believes that Iran is attempting to build a nuclear weapon in violation of the global nuclear non-proliferation treaty, and it objects to North Korea's nuclear weapons stockpile and exports of nuclear materials and technology.
Binyamin Netanyahu, the Israeli prime minister, will not attend the conference and is expected to send Dan Meridor, the deputy prime minister, in his place.
Insiders said Netanyahu was worried Turkey and Egypt would use the summit to challenge him over his country's nuclear arsenal, which Israel has never officially acknowledged.
The two countries likely planned to demand that Israel sign up to the 1970 Non-Proliferation Treaty (NPT).
The conference is the fourth leg of Obama's campaign to rid the world of nuclear weapons, which began a year ago in Prague in the Czech Republic, when he laid out plans for significant nuclear reductions.
Last week Obama approved a new nuclear policy for the US vowing to reduce its' nuclear arsenal, refrain from nuclear tests and not use nuclear weapons against countries that do not have them.
North Korea and Iran were not included in the pledge.
Also last week Obama and Dmitri Medvedev, the Russian president, signed a new START treaty that reduces each side's deployed nuclear arsenal to 1,550 weapons.
The conference is a precursor to the United Nation's Non-Proliferation Treaty review conference next month, seen as another important moment in heading off a future nuclear arms race.