According to the FAA, a Learjet 55 departed from Northeast Philadelphia Airport en route to Springfield-Branson National Airport in Missouri when it went down.
Police say the plane was on a medical assignment. The FAA and Secretary of Transportation Sean Duffy said six people were on board.
In addition to four crew members, there were two passengers, including a pediatric patient, according to Jet Rescue Air Ambulance, a company based in Mexico that provides global air ambulance services.
"At this time, we cannot confirm any survivors," the company said in the statement. "No names are being released at this time until family members have been notified. Our immediate concern is for the patient's family, our personnel, their families and other victims that may have been hurt on the ground."
Speaking at a news conference shortly after 8:30 p.m., Philadelphia Mayor Cherelle Parker said officials could not yet provide a number of fatalities.
"So right now we're just asking for prayers," she told reporters.