A mortar round struck the roof of the nunciate in the central part of the city early Tuesday, damaging the building but causing no injuries, Vatican Radio said.
"We do not know why it happened. We cannot say the Vatican embassy was targeted," said Archbishop Mario Zenari, the apostolic nuncio to Syria.
Zenari said the international community needs to strengthen its efforts to end the conflict in Syria.
"The Syrian people want the violence should stop immediately. They are fed up with this conflict," he said.
Discussions began in Switzerland among the U.N.-Arab League envoy to Syria and U.S. and Russian diplomats on the delayed Syria peace talks. Wrangling over agenda items and who will attend have held up the Geneva peace conference negotiators have been trying to finalize for months, the BBC said Tuesday.
U.N.-Arab envoy Lakhdar Brahimi also will meet delegates from the rest of the U.N. Security Council and Syria's neighbors.
The United States remains committed to the Syria peace summit despite the obstacles "because political reconciliation, a political negotiated solution, is the only way out of the bloodshed in Syria," White House press secretary Jay Carney said during a media briefing Monday.
He reiterated the U.S. position that Syrian President Bashar Assad cannot be part of his country's future because he "long ago relinquished that opportunity because of the actions he took and the amount of his own people's blood he has spilled."
Dozens of senior diplomats were in Geneva to discuss peace negotiations, but officials from Syria's government and opposition groups were absent and still disagree on the parameters and conditions of the discussions, the BBC said.
In Moscow, Russian Foreign Minister Sergei Lavrov said Iran, one of Syria's key allies, must be among those invited to the peace talks.
Meanwhile, the United Nations said the number of Syrians in need of aid has skyrocketed, the BBC reported.
Aid agencies have warned more than 9 million Syrians need humanitarian relief.
The United Nations estimated more than 2 million people have fled Syria since the unrest began in March 2011 and more than 100,000 people have been killed.