Words of warning and defiance are expected when US President Barack Obama, Iran's leader Mahmoud Ahmadinejad and Israel's Prime Minister Benjamin Netanyahu join more than 120 heads of state and government at the UN General Assembly.
Because of international divisions over the 18-month-old Syria conflict, the UN is holding no formal meeting on the civil war.
But Obama and Western leaders are expected to call for action in their speeches. The US president is one of the first speakers on Tuesday after the event is opened by UN Secretary-General Ban Ki-moon.
"We're going to have to work to prevent Iran from getting a nuclear weapon," Obama said previewing his speech Saturday. "We're going to have to make sure that not only our diplomatic posts are safe, but we go after folks who threaten or try to kill Americans."
Ban and UN-Arab League envoy Lakhdar Brahimi agreed in talks Saturday that the conflict is a "steadily increasing threat to regional peace and security," a UN spokesman said. And the Syria campaign will be pressed outside the General Assembly. Brahimi will brief the UN Security Council on Monday on his talks with President Bashar al-Assad.
Syria will also dominate a Security Council ministerial debate on links with the Arab League on Wednesday, the European Union is set to launch a new appeal for humanitarian funds and a Friends of Syria ministerial meeting is planned for Friday.
Diplomatic wounds over Syria are not close to healing. Neither Russia nor China, which have three times vetoed Security Council resolutions on Syria, will be represented by a senior leader in New York. Assad is expected to send his foreign minister.
"Everyone will be thinking about Syria, talking about Syria, but there will be no decision and no major progress," said one senior UN diplomat, speaking on condition of anonymity.
Stewart Patrick, an expert on international institutions and global governance for the Council on Foreign Relations think-tank, said that Syria will be one of two "lightning rod" issues at the summit with the Iran nuclear showdown.
Ahmadinejad is in New York for probably his last appearance at the General Assembly. This time there is feverish speculation that Israel is planning a military strike on bunkered Iranian nuclear facilities that Tehran insists are for peaceful purposes, but Western nations say hide attempts to develop a nuclear bomb.
Ahmadinejad speaks to the assembly on Wednesday, when a new walkout is predicted if the Iranian leader repeats one of his toxic remarks about Israel.
Top officials from Britain, China, France, Germany, Russia and the United States -- which are attempting to negotiate with Iran -- are to meet on Thursday just after Israel's prime minister addresses the assembly.
Netanyahu and Obama will not meet in New York and this has heightened speculation of a rift between the two. The United States and its allies have stepped up warnings to Iran, however, that time is running out for a negotiated solution to the showdown.
Netanyahu will take the UN stage two slots after Palestinian president Mahmud Abbas. Last year, Abbas took center stage with his emotional bid for full membership of the UN, which was thwarted by the United States.
Abbas is this time expected to announce that the Palestinians will seek elevated observer status, a move that neither the United States nor Israel can block but that is only a second prize.
The deadly protests in Muslim nations against an Internet video made in the United States that mocks Islam will also receive much attention.
Muslim leaders will reaffirm their anger in their speeches and the film will top the agenda at a meeting of foreign ministers from the 57-member Organization of Islamic Cooperation on Friday.
OIC Secretary General Ekmeleddin Ihsanoglu told AFP that world leaders must "come together in solidarity and as a political gesture and show of goodwill" to condemn the film and "to underline the ethical responsibility of all to respect human dignity and not to insult the 'other' over most sacred values."
He said leaders must break "the vicious circle of provocation and violent reaction instigated by the marginal extremist forces of the societies on both sides of the so-called divide."
The week-long debate for world leaders will also see key meetings on the conflicts in Mali, Democratic Republic of Congo, Somalia and Yemen.