About 600 government officials, businesspeople, environmental activists and academics are expected at the two-day Our Ocean conference in the Central American country.
At a meeting ahead of the summit, representatives of the European Union, the United States, Latin America and the Pacific Islands called on the treaty on the high seas, which has been under discussion at the United Nations for more than 15 years, to be signed as soon as possible.
"Let's seal the agreement," said France's Secretary of State for the Sea, Herve Berville.
"We are very close," said Maxine Burkett, US Deputy Assistant Secretary for Oceans, Fisheries and Polar Affairs.
At the conference, the EU pledged "strong engagement for international ocean governance" backed by funding of 816.5 million euros this year.
The high seas, which are not under the jurisdiction of any country, represent more than 60 percent of the oceans and nearly half of the planet.
UN Secretary-General Antonio Guterres called on Wednesday for negotiators from member states to conclude a "robust and ambitious" treaty on the high seas.
"Our ocean has been under pressure for decades. We can no longer ignore the ocean emergency," he said.
Topics on the Panama agenda include expanding marine protected areas (MPAs), assuring a sustainable ocean-derived "blue economy", and reducing stressors on an invaluable but at-risk resource.
The conference's opening panel will feature John Kerry, a former US secretary of state who was appointed as White House special envoy for climate.
Delegates will be under pressure to turn rhetoric into action.
Since the first conference in 2014, participants in over 70 countries have announced commitments worth more than $108 billion and protected more than five million square miles of ocean, according to organizers.
The conference "is key to maintain political will on ocean action," according to Courtney Farthing, policy director at Global Fishing Watch.
By bringing governments, activists and industry together, "we are able to increase our collective understanding of the issues our ocean is facing and successful initiatives that could be more widely adopted," she told AFP.
Observers say the Our Ocean gathering is important because it is the only conference to address all ocean-related issues under a single roof.
It also serves as a public stage for governments, through senior ministers in attendance, to put on a show of political will.
The meeting takes place with multinational companies eyeing minerals on the ocean floor.
These include so-called manganese nodules, settled on the seabed, that contain metals critical in battery production.
Environmentalists say harvesting them would be devastating for deep-sea ecosystems.
"There isn't really a big extraction today, but there is a significant advance in technology and machinery to eventually extract minerals, mainly rare minerals," said Maximiliano Bello of non-governmental organization Mission Blue.
Conference delegates will not adopt agreements or vote on proposals, but rather announce voluntary "commitments" to ocean protection.
Covering three-quarters of the Earth, the oceans are home to 80 percent of all life on the planet, and provide nourishment for more than three billion people as well as a crucial avenue for global trade.