Mental illness and substance use disorders are prevalent among workers. Each year businesses lose billions of dollars to decreased work performance associated with these issues. This article discusses a theoretical model that depicts relationships between social discrimination, job concerns, and social support and workers' mental health problems and substance use and work performance. The focus is Asian immigrant workers, a population underrepresented in the literature. This model serves to assist occupational health nurses in the practice and research arenas better understand the complexities of mental health problems and substance use among Asian immigrant workers. Occupational health nurses are in a prime position to recognize, identify, and respond to at-risk workers. Examples of areas that might be considered by occupational health nurses when using this model are included.