"Even with the Cold War over, the spread of nuclear weapons or the theft of nuclear material could lead to the extermination of any city on the planet," Obama told world leaders at the summit.
The US president has travelled to Prague, the Czech capital, after the conclusion of the Nato summit co-hosted by France and Germany.
Speaking aboard Air Force One on Saturday, Denis McDonough, the US deputy national security adviser for strategic communications, said that Obama's vision of a world without nuclear arms was an achievable goal.
"Tomorrow [Sunday], I think you'll hear the president, in a very comprehensive way, outline many of the things that he's been talking about and working on for some time," McDonough said.
Avner Cohen, an expert on nuclear non-proliferation, told Al Jazeera: "There is an obligation under the non-proliferation treaty to move in the speediest way towards disarmament. [However] this was never taken seriously.
"I think this is an effort to try and give that some concreteness.
"I think it is important if we are coming to Iran and North Korea [about their nuclear programmes] we need to keep up our part of the obligation."
Thousands of Czechs are expected to turn up for Obama's speech at a square outside the medieval Prague Castle.
Last week, Obama met Dmitry Medvedev, the Russian president, on the sidelines of the G20 economic summit, where the two leaders pledged to pursue a new deal to cut back on nuclear warheads.
While in Prague, Obama will also discuss climate change and energy security with the 27 leaders of European Union countries.
The Czech Republic, a close US ally that has sent troops to Iraq and Afghanistan, currently holds the EU presidency, but its leadership was undermined by a government collapse last week.
The cabinet of Mirek Topolanek, the prime minister, is expected to leave power soon.
Topolanek is expected to ask Obama about US plans to build a missile defence radar southeast of Prague, a project firmly backed by the Czech government but opposed by most Czechs.
The US plan has also angered Russia.
Obama has told Moscow he is willing to slow the deployment of the system in Europe if Russia helps in curbing Iran's nuclear ambitions.