Substance abuse and addiction are a major burden to society, both in financial costs and public health. Biologic and psychosocial differences in substance misuse exist between sexes. These differences influence the prevalence, presentation, comorbidity, and treatment of substance use disorders and suggest that a tailored and personalized approach should be developed specifically for women. Likewise, mental illness in women who also have a substance use disorder is common. This understudied and undertreated population represents a population that is vulnerable to poor mental and physical health outcomes. This paper will briefly examine the importance of addressing treatment specifically tailored to women and will discuss the further implications of substance abuse in women who have severe mental illness. Future pharmaocologic and psychosocial treatments should be tailored for women, particularly those who are dually diagnosed.