Romain was working as a florist when her boss suggested she pose in nude magazines. She was discovered by the Floyd Agency, an adult industry talent agency, while working for a tourist magazine in 2001. In August 2005, she moved to the United States. That same year, she signed with the agency LA Direct Models.
In the period from 2005-2007 Sandra Romain released more than one hundred movies per year, yielding her nominations for the AVN Female Performer of the Year Award in 2006 and 2007. She took a four-year hiatus from performing and returned to the adult industry in 2011. Over the course of her prolific career, Sandra Romain starred in over three hundred Anal Sex scenes, leaving behind a record-breaking catalog of her work.
Romain was married to pornographic actor Paul Popescu for 17 years. They divorced on November 19, 2012. She has a sister, Alice Romain, who is also a pornographic Actress.
