More movie roles followed. In 1996 Rose had a small role in Bio-Dome as Denise, an environmentally conscious party girl. In the trippy and crazy Kiss & Tell, she portrayed Denise. McGowan’s rising star caught the eye of Wes Craven and he cast her as Tatum Riley in Scream, a movie that would be a huge success and re-evoke the slasher genre. Rose’s Tatum was a witty and sassy teenager, who met her demise at the hands of the killer. Although getting killed off meant no roles in the sequels, Tatum’s memorable death scene surely made film history and the performance gained more name to the rising actress.

Rose next went on to star as George in Lewis & Clark & George (1997). The film premiered at the Sundance Film Festival and never did gain wide release but her unforgettable performance as the silent con artist George still remains one of the fan favorites. McGowan also had a supporting role in Going All the Way and a cameo in Araki’s Nowhere. She also portrayed Miriam in short film Seed, of which Rose said: "It's the favorite thing I've done lately.”

The press immediately fell in love with McGowan because of her photogenic beauty, sharp intelligence and sarcastic sense of humor. Her publicist suggested that she should tone it down for the media but Rose kept on doing her own thing. She graced the covers of several magazines, including multiple times in Interview and Bikini and was featured on the sexiest women lists of men’s magazines all over the world.