Although day laborers are highly visible, as they seek employment, in public street corners or storefronts, their life struggles, including their mental health and social service needs, remain largely unknown to local officials or service providers. This is one of the first studies to directly examine the risk and protective factors impacting Latino Day Laborers’ (LDLs) well-being and substance use and abuse. The study utilized a mixed methods (qualitative and quantitative) design. Specifically, this study used risk and protective variables identified by LDLs in the initial qualitative phase of the study to quantitatively examine the impact on these factors on LDLs’ well-being and substance use and abuse. Based on a sample of 147 LDLs, the quantitative results indicate that risk factors for well-being include psychological distress, social isolation, and older age; while factors protective of well-being include higher levels of religiosity and sending remittances to family members. In addition, psychological distress was found to be a risk factor for substance abuse. A member checking focus group was conducted to contextualize and validate the quantitative findings with the lived experiences of LDLs. Implications for practice and policy are discussed. / text