US forecasters said Isaac was expected to be near hurricane strength when the eye of the storm makes landfall in Haiti, where hundreds of thousands of people are still living in squalid, makeshift camps with nothing but sheets of metal or tarp as roofs.
Early Saturday, the storm was "getting better organized" as it approached Haiti's southeastern coast, the US National Hurricane Center (NHC) said. It packed winds of nearly 110 kilometers (70 miles) an hour, with higher gusts.
Around 400,000 people still live in temporary tent camps following the earthquake that killed 250,000 and leveled Port-au-Prince, and they have nowhere to go.
The streets grew empty, and only a few, rare vehicles ventured out after dark. Earlier in the day, long lines had formed outside supermarkets as people stocked up on supplies.
"We're not ready," said Martine, who heads a watch group at a camp hosting a thousand families.
"When it rains, we stand under tents with holes in them. There are many children and we don't know what to do if we have to evacuate," she told AFP.
With no access to public restrooms or safe drinking water, residents of the Canape Vert camp complained about the lack of help from the authorities.
But a government official said President Michel Martelly, who canceled a
trip to Japan, had toured emergency shelters in central Port-au-Prince to distribute food supplies and blankets.
Prime Minister Laurent Lamothe said the entire government, including security forces, has mobilized to prepare for the storm.
Aid groups warned that those without proper shelter after the quake were among the most vulnerable if Isaac hits the capital, at risk of disease from water contamination and other disaster scenarios.
"We must now avoid any risk of a cholera outbreak by following proper hygiene," said Lea Guido, representative of the Pan American Health Organization and World Health Organization in Haiti.
A hurricane watch was in effect for Haiti, and a tropical storm warning was in effect for the neighboring Dominican Republic and eastern Cuba. A tropical storm watch was in effect for the Florida Keys and parts of south Florida.
The Haiti director for Oxfam said that his group was preparing clean water and hygiene kits to help prevent the spread of cholera and other water-borne diseases.
"Nothing short of a miracle can keep people safe from this kind of storm when their only shelter is a tent," said Oxfam's Andrew Pugh.
"Haiti's disaster preparedness and response capacities have improved since the earthquake, but much remains to be done to help the poorest people cope with hurricane-strength threats."
Isaac was just 100 kilometers (65 miles) south-southeast of Port-au-Prince as it swirled toward Haiti at 22 kilometers (14 miles) per hour, the NHC said. Its maximum sustained winds were clocked at 100 kilometers per hour.
The storm could dump up to 20 inches (51 centimeters) of rain on Hispaniola, the island Haiti and the Dominican Republic share. "These rains could cause life-threatening flash floods and mudslides," the NHC said.
After striking Haiti and southeastern Cuba, home to the US naval base and "war on terror" prison at Guantanamo Bay, Isaac was due to head Sunday for the Florida Keys off the southern tip of the United States.
In Cuba, the government declared a state of alert in the island's six eastern provinces, where nearly five million people live.
Local authorities "must understand the possible impact of the intense rain on dams, canals and rivers," the Cuban civil defense office said, warning of blocked water drainage systems and flooded roads.
Isaac could reach Florida just in time for the Republican Party's National Convention.
Tens of thousands of people from around the country will descend on Tampa for four days for the formal nomination of former Massachusetts governor Mitt Romney to challenge President Barack Obama in the November 6 election.
City officials have urged residents to prepare for the worst, and Republican National Committee chairman Reince Priebus has expressed concern about the storm but insisted the show would go on.
In the Gulf of Mexico, oil and gas operators braced for the storm, with BP evacuating its Thunder Horse platform, the world's largest offshore production and drilling facility.