The crash happened around 9:15 p.m. Sunday in the 1500 block of I-10, north of downtown, Houston police said.
Officers received calls about a woman begging for help on the side of the freeway, north of downtown.
Investigators said the victim was walking north or southbound on the mainlines when she was struck by a vehicle traveling eastbound.
The driver did not stop to provide medical assistance and fled the scene, police said. Investigators did not have a description of the suspect's vehicle.
The woman was alert when she was transported to Ben Taub Hospital, but later died due to her injuries, police said.
Anyone with information on the wanted vehicle or the driver is urged to contact the HPD Hit and Run Unit at 713-247-4072 or speak anonymously to Crime Stoppers at 713-222-TIPS.