De Mol became a researcher for the Belgian National Fund for Scientific Research (FNRS), obtaining a permanent position there in 1981 and becoming a director of research in 1996. Meanwhile, she had obtained a habilitation from the Université libre de Bruxelles; her habilitation thesis was Super-résolution en microscopie confocale. In 1998 she gave up her position with the FNRS, becoming an honorary researcher with them, to become a full professor at the Université libre de Bruxelles. She was head of the mathematics department at the university for 2009–2010, and chair of the Society for Industrial and Applied Mathematics Activity Group on Imaging Science for 2012–2013.