Nobel peace laureates as well as top United Nations and Nato officials will take part in the meeting on November 10th and 11th in the tiny city state, which will include an address by Pope Francis.
The Argentine pontiff is "working hard to promote the conditions for a nuclear-free world", Vatican spokesman Greg Burke said Monday, while denying press reports that the conference represented a mediation effort by Francis.
The meeting will include the personal testimony of a survivor of the atomic bombing of Nagasaki in Japan.
Archbishop Silvano Tomasi, the Holy See's permanent observer to the UN, who often speaks for the pope on the nuclear issue, said it was "clear we are facing a real risk of the use of atomic weapons".
It could happen "by chance, by choice, or because those sitting in the rooms with the buttons are unbalanced," he said in an interview with La Repubblica daily.
"Working to make sure our security is guaranteed not by weapons of mass destruction, but by the fact that nobody can use them, has become increasingly urgent," he added.
North Korea in recent months has sparked global alarm by conducting a sixth nuclear test and test-launching missiles capable of reaching the US mainland, while US President Donald Trump and the North's young ruler Kim Jong-Un have traded threats of war and personal insults.