The president has set a goal of ensuring all nuclear materials worldwide are secured from theft or diversion within four years.
On the table, too, will be Iran's perceived attempts to build a nuclear weapon in violation of the global Nuclear Nonproliferation Treaty, and North Korea's nuclear weapons stockpile and exports of nuclear materials and technology.
"We want to get the world's attention focused where we think it needs to be with these continuing efforts by al-Qaida and others to get just enough nuclear material to cause terrible havoc, destruction and loss of life somewhere in the world," Secretary of State Hillary Rodham Clinton said in an interview broadcast Sunday on ABC's "This Week."
Clinton said the gathering would be the largest assembly of world leaders hosted by an American president since the 1945 San Francisco conference that founded the United Nations.
Obama hopes to set the tone with one-on-one meetings Sunday with the leaders of India and Pakistan -- antagonistic, nuclear-armed neighbors -- as well as South Africa and Kazakhstan, which have given up nuclear weapons programs.
"These meetings will be an opportunity for the president to underscore the grave danger of nuclear terrorism to global security, while also addressing a range of bilateral issues with each country," said Ben Rhodes, a deputy national security adviser.
Iran and North Korea were not invited because they are viewed as violators of the nonproliferation agreement. Syria was left off the invitation list because the U.S. believes Damascus also has nuclear ambitions. An Israeli airstrike in 2007 destroyed what Washington claims was a nearly completed nuclear reactor designed to make plutonium.
Iran's nuclear program likely will come up as Obama pushes for a U.N. Security Council resolution calling for additional sanctions against Tehran.
Israel, meanwhile, said last week that Prime Minister Benjamin Netanyahu would not attend the conference as planned. Insiders said he was worried Turkey and Egypt would use the summit to challenge him over his country's nuclear arsenal, which the Jewish state never has acknowledged. In Netanyahu's absence, Israel will be represented by Deputy Prime Minister Dan Meridor.
Obama opens the conference Monday with a working dinner, and meets individually that day with the leaders of Jordan, Malaysia, Armenia and China. The sessions close Tuesday with a joint statement on efforts to prevent the transfer of nuclear materials and technology and to keep them locked up.
The Washington conference is the fourth leg of Obama's campaign to rid the world of nuclear weapons, which have been used only by the United States to force a Japanese surrender in World War II. The high-flown goal, which the president admits likely will not be reality in his lifetime, began a year ago in Prague when he laid out plans for significant nuclear reductions.
In the meantime, he has approved a new nuclear policy for the United States, vowing last week to reduce America's 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 that pledge because they do not cooperate with other countries on nonproliferation standards.
That was Tuesday, and two days later, on the anniversary of the Prague speech, Obama flew back to Prague where he and Russian President Dmitri Medvedev signed a new START treaty that reduces each side's deployed nuclear arsenal to 1,550 weapons. Both the Russian parliament and the U.S. Senate still must approve the agreement. Obama wants the Senate to ratify the agreement this year, but Sen. Lamar Alexander, R-Tenn., said on "Fox News Sunday" that would not happen because of unanswered questions about the treaty and more pressing issues facing the Senate.
Medvedev arrives Monday to sign a long-delayed agreement to dispose of tons of weapons-grade plutonium from Cold War-era nuclear weapons -- the type of preventive action Obama wants the summit to inspire. Gary Samore, Obama's top adviser on limiting the spread of nuclear weapons, said a number of countries are expected to announce Monday unilateral measures toward that goal. The actions might include retrofitting reactors to use fuel harder to convert to weapons material or agreeing to sign international conventions on nuclear security.
The 1980 Convention on the Physical Protection of Nuclear Material, for example, was amended in 2005 to require states to protect such materials even when not in transit. The convention also expands measures to prevent nuclear smuggling. Not enough countries approved the 2005 amendment to put it into force. At the summit, Obama hopes to persuade balking countries to sign on.
Last week Obama said nuclear terrorism poses a graver danger than the risk of war between nuclear nations. And Ben Rhodes, a deputy national security adviser, said the threat of nuclear-armed terrorists is urgent.
"We know that terrorist groups, including al-Qaida, are pursuing the materials to build a nuclear weapon and we know that they have the intent to use one," Rhodes said.