The kings and emirs, gathering in Saudi Arabia, are expected to voice support for a bid to unify Syria's opposition at separate talks due to get under way on the same day in Riyadh.
The Gulf Cooperation Council (GCC) summit also comes days before warring factions from Yemen are to gather in Switzerland in an effort to end a costly war that has drawn in Gulf nations.
The GCC brings together Bahrain, Kuwait, Oman, Qatar, Saudi Arabia and the United Arab Emirates, whose leaders will hold two days of talks in the Saudi capital.
But despite the urgency of the challenges facing the six countries, analysts say the Gulf monarchs will struggle to find common ground at the gathering.
"This summit comes as the Gulf is witnessing one of its most critical years," said Farea al-Muslimi, a visiting scholar at the Carnegie Middle East Center.
He sees "internal disagreement" among the Gulf states as they face complicated economic and security challenges.
These include greater worries about Iran after a July deal that will ease sanctions on the predominantly Shiite nation, including its oil sector, in return for restrictions on its nuclear facilities.
Iran and Sunni-dominated Saudi Arabia are rivals for regional influence in Yemen, Syria and elsewhere.
"The main challenge facing the GCC summit is, as usual, trying to ensure a united front on the major strategic challenges in the region," said Neil Partrick, author of a forthcoming book on Saudi foreign policy.
BID FOR UNITY
The summit coincides with Saudi Arabia's hosting -- also on Wednesday and Thursday -- of talks it hopes could help ease out Syria's President Bashar al-Assad.
About 100 representatives from Syria's fragmented political and armed opposition groups -- including radical Islamists -- are gathering in Riyadh in an unprecedented bid for unity ahead of potential negotiations with Assad's regime.
The effort precedes peace talks targeted for January 1 under a plan for political transition in Syria. Diplomats from 17 countries including Saudi Arabia agreed on the plan last month.
Partrick said that with Saudi Arabia and Qatar competing to support Syrian rebel groups, the GCC summit is unlikely to offer much, except "broad support" for the opposition and conditional talks with the Assad administration.
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Those GCC divisions mean that a clear line on who should represent the rebels is not expected, he said.
Assad is supported by Iran and Russia, which has for more than two months been conducting air strikes in Syria.
Saudi Foreign Minister Adel al-Jubeir said in late November that if Assad does not step down peacefully "he could be ousted militarily".
For more than eight months, Gulf military forces have been fighting in Yemen to support President Abedrabbo Mansour Hadi's government alongside an array of local anti-rebel forces.
The coalition has been trying to push Iran-backed Shiite Huthi rebels and allied troops from territory they occupied in Yemen.
Jihadists have taken advantage of the chaos to expand their presence.
'EXPECT VERY LITTLE'
Oman is the only GCC state not part of the coalition but has mediated and provided a neutral venue for talks.
"On Yemen expect very little" from the summit other than support for Hadi's "legitimacy", said Partrick.
According to the United Nations envoy to Yemen, another attempt at peace talks will start on December 15, after earlier efforts collapsed.
Jane Kinninmont, of the Middle East and North Africa programme at the Chatham House think-tank in London, said divisions have weakened the GCC's ability to work together on solutions to regional crises.
Gulf rivalries which "exacerbated the factionalism in Syria's opposition" are one example.
"They need a clearer common line on some of the key regional threats," Kinninmont said.
The GCC was founded to more deeply integrate the Gulf countries but Kinninmont said the emphasis over the last few years has been on intelligence and security cooperation.
Low oil prices "should focus the minds of GCC leaders" on economic integration and joint infrastructure development, in line with the wishes of many Gulf citizens, she said.
Crude prices have more than halved since early 2014 and the IMF has projected a $275 billion drop in export revenues this year for the resource-dependent Gulf economies.