[1] Shafi entered the modelling industry at the age of 17, when she starred opposite Jawad Ahmed in the music video for the song "Bin Teray Kya Hai Jeena".
Her portrayal of Laxmi, an Indian spy agency Research and Analysis Wing's operative was critically praised by the Pakistani media.
Shafi sang along with the internationally acclaimed folk singer Arif Lohar on Coke Studio Pakistan Season 3, with the song "Alif Allah (Jugni)".
The single, originally composed and performed by Lohar, gathered over 20 million+ views on YouTube, was the most-viewed Coke Studio song ever, until it was overtaken by "Tajdaar-e-Haram", and was used in several films like Cocktail, Diary of a Butterfly and Jugni.
In 2014, Meesha Shafi returned to the Coke Studio floor for a third time to perform "Sun Ve Balori" with the composer and tabla guru Ustad Tafu and producers Strings.
In August 2015, she released 'Mehram Dilaan De Mahi' for the OST of the biopic (directed and portrayed on screen by Sarmad Khoosat), based on the life and works of prose writer, Manto.
In April 2013, Shafi joined Strings, Ali Azmat, Shahzad Hasan and Alamgir as a judge and mentor on the singing talent show Cornetto Music Icons, aired on ARY Digital.
Meesha's case helped in spotting out loophole in Pakistani justice system according to which a woman cannot make harassment allegations against someone unless she's employed by the accused party.
[11][12] Shafi won an appeal against Lahore High Court's decision to stop her defamation case in favor of Zafar's on 19 January 2022.