Nithya Menen made her acting debut as a child actor in the 1998 Indian-English film titled ‘The Monkey Who Knew Too Much.’ In 2006, she starred as ‘Anu’ in the Kannada romance film ‘7 O’Clock.’ The year 2008 saw the release of the Malayalam film ‘Aakasha Gopuram’ where Menen played the role of ‘Hilda Varghese.’ Even though the film could not do well at the box office, Menen’s performance was well-received by the critics. In 2009, she starred in the Malayalam-language anthology film ‘Kerala Cafe.’ The film opened to a positive response from critics. That same year, she was also seen in the Kannada language romantic film ‘Josh’ directed by Shivamani. She played the role of ‘Meera’ in the film which earned a ‘Filmfare Awards South’ nomination.
The year 2011 saw 6 releases of Menen, including the critically acclaimed Malayalam-language period action film ‘Urumi’ and the Tamil-language romantic drama film ‘180’ which marked her official Tamil debut. The following year, she starred as ‘Shahana’ in the Malayalam-language drama film ‘Ustad Hotel.’ The film was a critical and commercial success and came to be regarded as one of the best films made during the New-Gen cinema movement. The same year, Menen also appeared as ‘Priya’ in the Telugu romantic drama film ‘Ishq’ which earned her the ‘CineMAA Award’ for ‘Best Actress (Jury).’
She then starred in films like ‘Bangalore Days’ (2014), ‘S/O Satyamurthy’ (2015), ‘Kanchana 2’ (2015), ‘24’ (2016), 'Janatha Garage' (2016), 'Mersal' (2017), 'Geetha Govindam' (2018), and 'Awe' (2018). In 2019, she made her Bollywood debut with the drama film ‘Mission Mangal’ directed by Jagan Shakti. The film received a thumbs up from critics and was a commercial success.
Menen was last seen in the Telugu-language romantic comedy film ‘Ninnila Ninnila.’ The film opened to a positive reception. She will be next seen in the upcoming Telugu language action thriller film ‘Bheemla Nayak’ directed by Saagar K. Chandra.