In 2005, D'Cruz was called for an audition by director Teja, but the project was cancelled.[7] She instead made her feature film debut in the Telugu language romance film Devadasu (2006), directed by Y. V. S. Chowdhary. She underwent acting classes with Aruna Bhikshu, before starting to work on the film. She recalls that during filming she felt "pressured [...] almost cried and didn't want to go further", but went ahead after her mother encouraged her, giving her "the lecture of a lifetime [...] at 3 am."[8] Upon release, critics were in praise of Ileana, particularly referring to her physique and looks; Jeevi of Idlebrain wrote that Ileana "makes a cool debut. She is good at histrionics and has a fabulous body any woman would love to possess. She has great legs and nice physique",[9] while a review from Indiaglitz noted that she "has chiseled features and a figure to die-for."[10] Devadasu, which also marked its lead actor Ram's acting debut, became the year's first major commercial success, eventually grossing around 14 crores,[11] whilst earning Ileana the Filmfare Award for Best Female Debutant.[12] She next appeared opposite Mahesh Babu in the action flick Pokiri in which she portrayed an aerobics teacher, who is harassed by a corrupt police officer.[13] The film was a huge financial success, emerging the highest-grossing Telugu film of all time until then, as well as Ileana's biggest commercial success so far.[14][15][16]
Later that year, she made her Tamil-language film debut in Kedi (2006). Although the film did not do so well at the box-office,[16] D'Cruz remained too busy to accept all the film roles offered to her.[17][18] Her Telugu film Khatarnak (2006) in which she acted opposite Ravi Teja did not do as well as expected, which has been attributed to her glamorous appearance not going down well with the audience.[16] She subsequently experienced a setback in her career as her following releases Rakhi (2006) and Munna (2007) proved critically and financially unsuccessful.[16][19]
D'Cruz's career took a turn for the better with the release of her well-received 2007 film Aata, acting opposite Siddharth.[16] She received favorable reviews for her performance as Satya, a college student who is on the run from the home minister's crooked son by whom she is targeted, when leading a protest and demanding punishment for his crimes.[20] Idlebrain described her as "gorgeous" and a "treat to watch to the eyes".[21] In 2008, she performed a lead role opposite Pawan Kalyan in Jalsa, directed by Trivikram Srinivas. In spite of opening to mixed reviews, the film turned out to become a high financial success. Ileana received largely positive remarks, with critics citing that she looked "pretty",[22] "damn cool",[23] and "every bit chic and stunning through out the film",[24] while being later awarded the Santosham Award, one of five awards for Jalsa,[25] and the South Scope Style Award,[26] besides garnering a nomination for the Best Actress prize at the 56th Filmfare Awards South. Her first 2009 release, titled Kick, was likewise declared a box office success,[27][28] becoming one of the highest-grossing films that year.[29] Later that year she starred in the films Rechipo and Y. V. S. Choudary's Saleem alongside Vishnu Manchu, both of which performed poorly at the box office.[30][31] Huduga Hudugi, her first Kannada film, became her only 2010 release; she performed an item number, "Ileana Ileana", in the film.
Ileana then essayed the female lead role in Shakti, opposite Jr. NTR, which whom she worked earlier in Rakhi. The high-budget socio-fantasy film was panned by critics and became a commercial failure.[32][33][34] She later admitted that the film was a "big disaster" and did not promote the film,[35] citing that the film's script had been changed during the shooting and that she could not "connect to the story".[36] Her next release was Nenu Naa Rakshasi, which marked her second collaboration with Puri Jagannadh, following the success of Pokiri. Her performance was received positively by critics; an Indiaglitz reviewer described her as a "pleasant surprise in the film" as she "cried, smirked, looked hot, grabbed sympathy and made faces that were apt to the scenes",[37] while cinegoer's reviewer cited that the film had "one bright spot, Ileana, she looks stunning and also like an accomplished senior to the hero."[38] She is currently shooting for her second Tamil venture, S. Shankar's Nanban, a remake of the hugely successful and acclaimed 2009 Hindi film 3 Idiots, with Ileana essaying the character originally played by Kareena Kapoor. She would also make her Hindi debut with the Anurag Basu directorial Barfee, as the role of a narrator starring alongside Ranbir Kapoor and Priyanka Chopra in lead roles