Giant plans to open a store at the location at Cottman and Bustleton avenues.
Construction is set to start in late March. The store is scheduled to open later this year.
Giant said it plans to hire 200 employees for the new store.
"With its diverse neighborhoods, people, and undeniable passion for food, there's no place quite like Philadelphia, and that's exactly why The Giant Company continues to invest in new stores across the city," Nicholas Bertram, president of The Giant Company, said in statement.
Bertram said the 67,000 square foot store will feature a new look, along with a beer & wine eatery, expanded plant-based offerings, and made-to-order meals.
The 2201 Cottman Avenue location will also offer a grocery pickup option.
Including Giant and Giant Heirloom Market, the company currently operates four stores in the city of Philadelphia.