Hassanandani is recognised for her portrayal of Anjali Salve Nanda in Kkavyanjali, Sanchi Virani in Kyunki Saas Bhi Kabhi Bahu Thi, Shagun Arora Raghav in Yeh Hai Mohabbatein and Vishakha in Naagin 3.

"[13] Her other releases that year were: Samurai with Vikram,[14] Sreeram with Uday Kiran and Thotti Gang with Prabhu Deva.

[15] Hassanandani expanded to Hindi films in 2003 with Kucch To Hai opposite Tusshar Kapoor, which was a box office failure.

[18] Following this, Hassanandani appeared in three Telugu films: Ninne Ishtapaddanu, Aadanthe Ado Type with Aryan Rajesh,[19] and Nenu Pelliki Ready with Srikanth.

"[23] In her last release of the year, she played the lead opposite Puneeth Rajkumar in Veera Kannadiga, her Kannada debut.

She played Anjali "Anjum" Salve Nanda, a middle-class girl marrying into a business tycoon's family opposite Rakshak Sahni and Eijaz Khan.

[29][30] In Koi Aap Sa, Hassanandani played a rape survivor opposite Aftab Shivdasani.

Taran Adarsh noted: "After making an impact in Silsiilay earlier this year, Natassha gets an author-backed role and the actor is only getting better, more dependable.

[33] From 2007 to 2008, she played Sanchi Virani in Kyunki Saas Bhi Kabhi Bahu Thi opposite Naman Shaw.

[42] Hassanandani established herself among the leading actresses of Hindi television with her portrayal of Shagun Arora Raghav in Yeh Hai Mohabbatein opposite Sumeet Sachdev and Karan Patel.

[46] She then made her Punjabi film debut with Yaaran Da Katchup in 2014 and in the same year she appeared in Ragini MMS 2, which was a box office success.

[49] Alongside Yeh Hai Mohabbatein, she continued to play supporting parts in Bahu Hamari Rajni Kant, Trideviyaan and Sajan Re Phir Jhooth Mat Bolo.

[54] She made her web debut in 2018 with Galti Se Mis-Tech, playing a married woman caught in technological glitches opposite Rithvik Dhanjani.

[58] Following a small hiatus due to her pregnancy, Hassanandani made her comeback with the Hindi film Maarrich opposite Tusshar Kapoor, where she played a police officer's wife.