Abstract : Substance abuse namely alcohol, tobacco and illicit drugs are equally prevalent among women, although it was predominant by men, previously. Furthermore, there is also a biological gender difference between men and women in overall understanding on this matter. The aim of this review is to explore the issues and challenges that experienced by the women with the prevention program on substance abuse. The epidemiology on substance abuse in women are seen increasing in trend majority in many parts of the world. Among the issues seen are dependency and health related problem which comprised of the communicable and non-communicable diseases, and socio-economic impact to individual, family as well as the community. Subsequently, to tackle these, prevention approach should be from top to bottom which includes the law and legislation with policies that may need to be empower and enforced, continuous education, multiagency approach and enhancement on the research, development and technology. Therefore, it can be seen all the variation occurred as the interplay of the gender, behavior and environment that lead to more impact on this vulnerable group. As a conclusion, substance abuse is a public health enemy. Thus, it is important for all level of stakeholders to work together to achieved better health among the women and free from substance abuse.