Mandzuka’s first public appearance came at the age of 12, when she was selected as a model for a New Year's edition of Greek magazine "Selides". Her first stage performance came one year later in Cyprus, at age 13, in a theatrical production of Alice in Wonderland. Mandzuka got her first movie role at age 15 in a movie called "Virtualna stvarnost" (Virtual Reality) for which she was cast for the lead role of Senka taking the center stage in the movie alongside legendary Serbian actor Dragan Nikolic and actress Sonja Savic. She received numerous domestic nominations and awards for her performance as a drug addicted teenager in this movie which was sponsored by the Serbian Ministry of Culture as a campaign for the fight against drugs in the youth population. She capped of her award season with the newcoming actress of the year award.

Her most popular performance came in 2001 with the lead female role of Kata in the Serbian hit movie Munje! (Dudes or Thunderbolts). The movie broke all theater attendance records in Serbia and propelled Mandzuka to stardom at the age of 19. The movie was the first Serbian mega blockbuster of the new millennium and is considered a cult movie. During this time she was also playing in the popular TV show Treci Kanal od Sunca (Third Channel From the Sun).

Wanting to concentrate on completing her education before fully pursuing an international career, she made several minor appearances in independent international movies such as Empire (2003), Hell Ride (2007) and 2:22 (2008).

She was the Reebok brand Ambassador in Serbia.