The incident happened just after 9:30 p.m. at Rhawn Street and Roosevelt Boulevard.
According to authorities, a male and female couple were panhandling and approached the driver of a white Jeep.
Words were exchanged, and the male panhandler sprayed insecticide in the face of the driver.
The driver then pulled out a gun and shot the male panhandler, who died at the scene.
Officials are now looking for the white Jeep Cherokee last seen fleeing the crime scene.
Anyone with information is asked to contact police.