[6][7] Menen started her career as a child artist, in the French-Indian English film, Hanuman (1998), playing the younger sister to Tabu's character.

[18] In 1998, Menen appeared first on-screen as a child in a French-Indian English film named Hanuman, at the age of 8, playing younger sister to Tabu's character.

She was in the midst of her 12th class exams when she was offered the role, after Mohanlal had spotted her on the front cover of a tourism magazine, Stark World Kerala.

[4][11] Her performance was well received, with critics writing that she shows "sparkle in her debut venture" and "makes her entry in an impressive role",[22] though the film was a financial failure.

The film received rave reviews,[23] and became a commercial success as well, with her performance garnering her a nomination in the Best Supporting Actress category at the 57th Filmfare Awards South.

[24] In 2010, she starred in the Malayalam films, Anwar and Apoorvaragam where she plays Nancy, a young girl who gets involved with two male students (Nishan and Asif Ali) who are later discovered to be con-artists.

[25][26] Menen's career marked a turning point in 2011, with the romantic comedy Ala Modalaindi, which was her maiden Telugu venture.

[27] Following Ala Modalaindi, she starred in Santosh Sivan's historical fiction Urumi as part of an ensemble cast.

[33] She portrayed a Chirakkal princess named Bala, playing the love interest of Prabhu Deva's character,[33] which gained positive remarks, with a Sify review claiming that she "looks pretty and is a scene stealer".

[34] Menen quoted that much of her character was based on "Santosh's perception of who I am", with Sivan stating that he had written that role for her and that only she could play it.

She also featured in V. K. Prakash's Kannada anthology film Aidondla Aidu where she played a young bride who is obsessed with making payasam for her new husband much to his chagrin.

[44] Menen won rave reviews and her first Filmfare Award for Best Actress – Telugu for playing a character with two shades in Gunde Jaari Gallanthayyinde opposite Nithin.

[56] Menen received immense praises for the a romantic film O Kadhal Kanmani, directed by Mani Ratnam.

Dulquer and Menen's on-screen chemistry was praised and she garnered her first Filmfare Award for Best Actress – Tamil nomination.

The film was opened to high critical acclaim, Deccan Chronicle wrote, "Nithya Menen shines in her role.

[66] Towards the end of the year, she starred alongside Vikram in science-fiction thriller Iru Mugan and received praises for her limited role.

[70] Her only release in 2017 was the Tamil film Mersal opposite Vijay, where she was praised for her role as a tough yet supportive wife, Firstpost noted, "Among the three actresses, it is Nithya Menen who makes an impression with her competent performance.

[82] In 2020, Menen starred alongside Udhayanidhi Stalin in Mysskin's Psycho, where she played Kamala Das, a foul-mouthed quadriplegic ex-police officer.

[85] Firstpost wrote, "The big surprise in the film is Nithya whose impishness in the story is unlike anything else that she has portrayed over the years, and her on-screen chemistry with Selvan is a delight.

She starred in Bheemla Nayak opposite Pawan Kalyan and Rana Daggubati, the film was a box office success.

[89] Ram Venkat Srikar stated, "Nithya's Suguna, surprisingly gets a few memorable moments, and she brings a certain level of warmness to Bheemla whenever she is on screen.

[95] Menen received rave reviews for the romantic drama Thiruchitrambalam opposite Dhanush, where she played his childhood friend Shobana.

Janani K stated, "If you give Nithya a meaty character, everyone else can sit back and admire her living the role with full of zest.

"[98][99] Her performance won her the National Film Award for Best Actress (tied with Mansi Parekh for Kutch Express).

First she played a restaurant worker in Kumari Srimathi, with Vinamra Mathur calling her performance "lively, spunky and vibrant".

[106][107] With no release in 2024, Menen started 2025 with Kadhalikka Neramillai, where she played an architect and single mother opposite Ravi Mohan.

[110] Ankur Pathak of HuffPost stated that Menen's filmography is "filled with experiments" and noted, "The actor has taken risks throughout her career.

"[5] Sangeetha Devi Dundoo of The Hindu said that she had "shown a natural flair for acting" and noted that she had worked in a variety of genres from breezy romance to period drama to out-of-the-box projects.

[111] Latha Srinivasan of The New Indian Express noted, "Nithya Menen slips into her character's skin with effortless ease.

Hemanth Kumar of Firstpost said, "There's always been an air of mystery about Nithya Menen, and when she talks, she's careful about how she articulates her thoughts and ideas.