She launched her own clothing line, Chick by Nicky Hilton in 2004 and has also designed a line of handbags for Japanese company Samantha Thavasa from 2002–2005. In 2007, she started her second line aimed at a more mature audience and higher pricepoint, called Nicholai, which had its debut fashion show for the spring/summer 2008 season on September 9, 2007 in New York City during Mercedes-Benz Fashion Week. The video and photos from the collection can be viewed at the MBFW website.

Nicky Hilton made her acting debut in National Lampoon's Pledge This!, which also featured her sister Paris Hilton. The movie was a straight-to-DVD and released on December 19, 2006. She also made a cameo in Pauly Shore Is Dead, with Paris. In 2003, Nicky and Paris were each offered a role in a reality show called The Simple Life, but Nicky rejected the part. However, Paris went through with it, and her best friend Nicole Richie was given the role that Nicky refused.

Hilton began her career as a fashion model. She has done several runway shows for major designers and is a regular model for Heatherette, along with her sister Paris; they usually open and close the runway shows. In 2005, Hilton, along with Kimberly Stewart, was the face of Australian underwear line Antz Pantz. Stewart remains contracted, however Hilton has since been replaced by Australian up-and-coming model Megan Maitland. Around this time, Hilton modeled for the cover of Lucire magazine for its New Zealand and Romanian editions.

• "Paris Hilton's British Best Friend" .... Herself (1 episode, 2009)
       - Episode #1.1 (2009) TV episode .... Herself
• Paris, Not France (2008) .... Herself
• "Entertainment Tonight" .... Herself (3 episodes, 2008)
  ... aka E.T. (USA: informal title)
  ... aka ET Weekend (Australia: weekend title)
  ... aka Entertainment This Week (weekend title)
  ... aka This Week in Entertainment (USA: weekend title)
       - Episode dated 20 May 2008 (2008) TV episode .... Herself
       - Episode dated 14 February 2008 (2008) TV episode .... Herself
       - Episode dated 2 January 2008 (2008) TV episode .... Herself
• MTV Video Music Awards 2006 (2006) (TV) (uncredited) .... Herself - Audience
• "The Simple Life" .... Herself (2 episodes, 2004-2006)
  ... aka Simple Life Goes to Camp (USA: fifth season title)
  ... aka The Simple Life 2: Road Trip (USA: second season title)
  ... aka The Simple Life: 'Til Death Do Us Part (USA: fourth season title)
  ... aka The Simple Life: Goes to Camp (USA: fifth season title)
  ... aka The Simple Life: Interns (USA: third season title)
       - Murrie Family (2006) TV episode .... Herself
       - Back in the Saddle (2004) TV episode .... Herself
• "Project Runway" .... Herself (1 episode, 2006)
  ... aka Project Runway 2 (USA: second season title)
  ... aka Project Runway 3 (USA: third season title)
       - Social Scene (2006) TV episode .... Herself
• "The Tyra Banks Show" .... Herself (1 episode, 2005)
       - Hook Me Up like a Star (2005) TV episode .... Herself
• "Good Morning Australia" .... Herself (1 episode, 2005)
  ... aka G.M.A. (Australia: short title)
       - Episode dated 30 September 2005 (2005) TV episode .... Herself
• "Sunrise" .... Herself (1 episode, 2005)
       - Episode dated 29 September 2005 (2005) TV episode .... Herself
• "Rove Live" .... Herself (1 episode, 2005)
       - Episode #6.34 (2005) TV episode .... Herself
• "I Want to Be a Hilton" .... Herself (1 episode, 2005)
       - Episode #1.2 (2005) TV episode .... Herself
• "Larry King Live" .... Herself (1 episode, 2005)
       - Episode dated 27 June 2005 (2005) TV episode (voice) .... Herself