The robbery happened around 11:15 a.m. at the Wells Fargo branch at 2005 Market Street.
According to the FBI and the Philadelphia Police Department's Violent Crimes Task Force, the suspect entered the bank and handed a teller a threatening demand note.
After obtaining an unspecified amount of cash, the suspect fled the area on foot.
The suspect is considered armed and dangerous.
Anyone with information is asked to call investigators at 215-418-4000.
A reward is being offered for information leading to an arrest, police say, and tipsters can remain anonymous.