Ian, which had been downgraded to a tropical storm, is now a hurricane again, the U.S. National Hurricane Center said Thursday.
Ian is "taking aim," the center said, "at the Carolinas and Georgia with life-threatening flooding, storm surge and strong winds."
Ian is predicted to approach the coast of South Carolina on Friday, with its center moving farther inland across the Carolinas on Friday night and Saturday.
Ian could slightly strengthen before making landfall Friday, forecasters said, but could "rapidly weaken over the southeastern United States late Friday into Saturday."
Ian has left a path of destruction in Florida, and U.S. President Joe Biden on Thursday pledged the federal government will do whatever has to be done to help Florida rebuild.
Speaking from the headquarters of the Federal Emergency Management Agency in Washington, Biden said he had spoken with Florida Gov. Ron DeSantis and approved his requests for an expedited major disaster designation.
He said that means the federal government will cover the costs of removing all debris and rebuilding public buildings. The federal government will also provide funds to help cover the costs of rebuilding homes and recovering property for those who do not have enough insurance.
Biden said Ian could prove to be the deadliest storm ever to hit Florida by the time its effects are finally determined.
At a news conference earlier in the day, DeSantis said the extent of deaths and injuries was unclear, as rescue workers were only starting to respond to calls after not being able to go out during the treacherous conditions. Rescue crews were working by land, sea and air to reach stranded residents.
DeSantis said more than 2 million people were without power, and the amount of water rising in Florida is "basically a 500-year flooding event.'
"We've never seen a flood event like this. We've never seen a storm surge of this magnitude. And it hit an area where there's a lot of people," DeSantis said.
Ian came ashore Wednesday near Cayo Costa as a strong Category 4 hurricane, with maximum sustained winds of nearly 250 kph, along with a powerful storm surge and heavy rains that combined to flood coastal areas.
The Collier County Sheriff's Office said it carried out at least 30 rescue missions Wednesday and cautioned residents that Thursday was likely to be "frustrating and heartbreaking for many" as people began to assess damage from the storm. The county was one of several that instituted overnight curfews.
Hurricane Ian earlier hit western Cuba, killing two people and leaving the entire island without power after its aging electrical grid, which has been struggling to remain operational amid a dire economic crisis, collapsed late Tuesday.
Ian left behind a trail of destruction across Pinar del Rio province, Cuba's main tobacco-growing region, ripping the roofs off homes and buildings and making streets impassable because of downed trees and power lines, and flooding.
Authorities evacuated as many as 40,000 people from low-lying areas of Pinar del Rio.
Some information in this report came from The Associated Press, Reuters and Agence France-Presse.