Sabeen Mahmud, the director of The Second Floor (T2F) cafe which organizes debates and art events, died on her way to the hospital.
Doctors said they retrieved five bullets from her body.
Her mother also sustained bullet wounds. She is said to be in critical condition, local media reported.
"Two gunmen on a motorcycle shot her. She was taken to hospital where she was pronounced dead," senior police official Tariq Dharejo said, adding police were investigating the killing.
T2F had organized a talk on Baluchi nationalists who often disappear in the country’s southwestern Baluchistan province.
Prime Minister Nawaz Sharif has condemned the incident and ordered an investigation.