Joe Biden has declared Hurricane Ian may have resulted in "substantial loss of life".
The US President said the storm continues to move across Florida and is possibly the deadliest the state has ever seen.
Speaking at the FEMA headquarters in Washington DC on Thursday afternoon, he said he could, however, only go off early reports as "the numbers remain unclear".
Mr Biden continued: “My message to the people of Florida and to the country: At times like this, America comes together. We’re going to pull together as one team, as one America.”
“However long it takes, we’re going to get there,” POTUS46 said, adding: “That’s my commitment to you.”
It comes as rescue workers and residents of Florida's Gulf Coast today searched for missing people and picked up the pieces from wrecked homes.
The howling winds, torrential rains and raging surf have caused major destruction, including massive power outages.
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Ian flooded communities before plowing across the peninsula to the Atlantic seaboard.
Local power companies said more than 2.5 million homes and businesses in Florida remained without power.
Governor Ron DeSantis said that Lee and Charlotte counties, home to more than 900,000 people, were "basically off the grid."
The storm blasted ashore at the barrier island of Cayo Costa on Wednesday afternoon as a Category 4 hurricane with maximum sustained winds of 150 miles per hour (241 kph).
It rapidly transformed Florida's southwestern shoreline, dotted with sandy beaches, coastal towns and mobile home parks, into a disaster zone as it swept seawater into waterfront homes.
"The impacts of this storm are historic and the damage that was done was historic," DeSantis said during a news briefing.
"We have never seen a flood event like this. We have never seen storm surge of this magnitude."
There were two unconfirmed storm-related fatalities, DeSantis said.
The extent of deaths and injuries remains unclear as rescue workers are only starting to respond to calls after not being able to go out during the treacherous conditions.
DeSantis said 28 helicopters were performing water rescues.
He also said the bridge to Sanibel Island - a barrier island on the Gulf coast - was severely damaged and impassible.
Two area hospitals were evacuated, with patients moved to higher ground.
In the early morning hours after it passed, residents and rescue workers in hard-hit areas like Venice, located in Sarasota County about 75 miles (120 km) south of Tampa, hunted for family and friends as trees, debris and power lines covered roads and standing water washed over the ground.
Kurt Hoffman, sheriff of Sarasota County, told residents in a Twitter post that there were more than 500 calls for help and that they are "triaging" them for the most urgent.
"Patrol deputies resumed operations a few hours ago & are responding to the highest priority calls first," Hoffman wrote.
"Sit tight, we know many of you need help."
The search for loved ones was made more difficult as cellphone services were often cut.
"A lot of down trees, a lot of flooding everywhere. We are trying to get a hold of my daughter," said Terri Byrd as she sat in a vehicle in a Walmart parking lot trying to get cell service after spending the night at an elementary school in Venice.
Ian, now a tropical storm, slackened as it trekked across Florida but was still producing strong winds, heavy rains and storm surge, including in Georgia, South Carolina and North Carolina, the U.S. National Hurricane Center said.
The storm, packing maximum sustained winds of 65 mph (100 kph), was about 40 miles (70 km) southeast of Orlando, the Miami-based forecaster said.
It was expected to reach the Atlantic Coast on Thursday afternoon, unleashing drenching rains and threatening to bring more extensive flooding.
Up to 30 inches (76 cm) of rain was forecast to fall on parts of central Florida, the hurricane center said.
Mr Biden said Federal Emergency Management Agency Director Deanne Criswell will be in Florida on Friday.
He also approved a disaster declaration, making federal resources available to the counties impacted by the storm.
The damages caused by Ian will turn out to be catastrophic and FEMA is preparing for potentially thousands of people to be displaced in the long-term, Criswell told CNN.
"I don't think that we can quantify it yet," Criswell said when asked about damages from the storm. "But I can tell you that it is going to be catastrophic."
She said FEMA was preparing for thousands of long-term displaced people in the region, as large population centers were hit as well as families living in mobile homes.
Some utilities had started to restore power for customers now that the storm has passed southern Florida but the number of outages increased as the storm moved across Florida.
Florida Power & Light Co (FPL) mobilized more than 13,000 personnel to support power restoration efforts.
