Lodhi was born in Karachi to Ali Gohar Lodhi and Roshan Taj Lodhi. She grew up in a family with three brothers (Amir Lodhi, Tahir Lodhi and Sahir Lodhi). She completed her MBBS from Jinnah Sindh Medical University.
Shaista started her career in 2001. She was the host of the morning show Good Morning Pakistan, which airs on Ary Digital. In the end of September 2010, she joined GEO and hosted a morning show Utho Jago Pakistan on the same channel. The show was suspended on 15 May 2014 by the channel administration after alleged blasphemy during the show and she left Pakistan because of fears for her safety. Shaishta moved to South Africa with her three children and returned to Pakistan in 2015 and made her come back in morning shows by hosting Sitare Ki Subah on Hum Sitaray.
Shaista has a brother Sahir Lodhi, who is also working in TV. She also hosted Mehmaan Nawaz on SEE TV and now hosting Geo Subah Pakistan on Geo TV.
In 2020, Shaista Lodhi was appointed the Peshawar Stallions in Jeeto Pakistan League in Ramadan Special.
She married for the second time in June 2015 after giving divorce to her first husband in 2012. Shaista married Adnan Lodhi and she has three children.