After teaming up on a succession of projects with Indian directors including Ram Gopal Varma and Ketan Mehta, Sen signed for one of the principal roles in the jarring, terrorist-themed American drama The War Within (2005), which premiered at the Toronto International Film Festival[5] and, in the process,[6] began to cultivate a reputation for being drawn to offbeat, challenging and demanding roles, often with a social or political theme.

Nandana has been actively fighting to stop the crisis of child trafficking in India,[14][15] both with organizations such as the NCPCR and the Terre des hommes foundation[15][16] as well as addressing this topic in cinema.

Her portrayal of Sugandha in Rang Rasiya (2008) has been hailed by critics as "pitch-perfect,"[23] "superb,"[24] "divine, elegant, and enticing,"[25] "innocent and vulnerable,"[26] "fearless, uninhibited,"[27] "radiant in every frame",[28] "poignant, lustrous",[29] "stunning"[30] and "as refined as it is bold".

[31] Sen's groundbreaking performance[27] as artist Ravi Varma's muse in this historical romance on the religious censorship of art subsequently won her the prestigious Kalakar Award for Best Actress in 2015: in her acceptance speech, Nandana went on record saying that the award honours "the greater cause of free speech and expression, now under enormous threat everywhere, as shown by the horrifying Charlie Hebdo killings in Paris.

[citation needed] Sen experienced her first taste of cinema acting while still a student when director Goutam Ghose tapped her to play the lead in his dark and disturbing psychodrama The Doll (Gudia)[45] as one of the targets of a middle-age man's sexual obsession, which premiered at the Un Certain Regard section of the Cannes Film Festival.

In the anti-war film Tango Charlie, Sen played the female lead opposite Ajay Devgan starring Sanjay Dutt and Bobby Deol and with Anil Kapoor in My Wife's Murder.

[52] In 2007, Sen signed on to portray a young rebellious woman fleeing from law authorities in director Shamim Sarif's lesbian-themed period drama The World Unseen.

In theatre as in film, Sen has often played an artist's muse and has been critically appreciated each time, including the off-Broadway production "Modigliani",[54] the Bengali blockbuster "Autograph",[38] and her latest release, "Rang Rasiya".

[55] A favorite cover-girl of leading magazines for women as well as men, such as Femina,[56] Savvy,[57] FHM,[58] Man's World[59] and Maxim,[60] Sen is known as much for her performances as for being comfortable with her sexuality and for speaking her mind:[citation needed] "My body is as much a part of my humanity as my brain, my morals, and my heart, and I will never be ashamed of expressing it with the dignity and self-respect it deserves.

[8] [5], "Every Word a Lifelong Quest" (Lithub, 2021)[6] and "Letter to Ma" (The Ink, 2021) [7] Sen married John Makinson, Chairman of Penguin Random House, in June 2013.