George started modeling in her early teens and in 1992 she was named Western Australia's Teenage Model of the Year. At age sixteen she was discovered by casting agent Liz Mullinar and got the role of Angel Parrish alongside Dieter Brummer on the popular Australian soap Home and Away. George left Perth and moved to Sydney to start her acting career. After three years on the show she decided to leave to try find other acting challenges. Melissa was featured nude in Australian Playboy and also in celebrity photo magazine Black + White shortly after leaving Home and Away.

George made a health and fitness video, Mind, Body and Soul (1996), created a sleepwear line named "An Angel at My Bedside" and had a recurring role on the short-lived television series Roar (1997), opposite Heath Ledger, before leaving Australia to move to Los Angeles to try her luck in the US. After moving to Los Angeles, she scored small roles in several films, including Dark City, The Limey, Mulholland Drive