Simultaneously with her Telugu debut, Samantha also debuted in Tamil cinema with 'Vinnaithaandi Varuvaayaa', which was also directed by Gautham Vasudev Menon. This was a remake of 'Ye Maaya Chesave'. Her role marked a promising start to her Tamil film journey.

Samantha received critical acclaim for her role in 'Neethaane En Ponvasantham', a Tamil romantic drama directed by Gautham Menon. Her nuanced performance earned her recognition and awards in the Tamil film industry, including the Filmfare Award for Best Tamil Actress.

Samantha appeared in several Tamil films, gaining significant recognition and a strong fan base. She starred alongside leading actors in Kollywood.

Samantha had a string of successful Tamil films, including 'Theri' with Vijay and '24' with Suriya. 'Janatha Garage', although a Telugu film, also released in Tamil, and did well. Her role in these commercially successful films added to her popularity.