Background: Little research has been conducted on relations between challenging working and living conditions and psychological distress in Latino migrant day laborers (LMDLs), a particularly marginalized Latino population in the United States. Aims: Consistent with a structural-environmental framework of LMDL vulnerability to health and mental health problems, this study tests a model of hypothesized pathways between working and living conditions and multiple forms of psychological distress. Method: Structural equation modeling was used to test the conceptual model with 344 LMDLs who participated in a cross-sectional survey in the San Francisco Bay Area. Results: As hypothesized, results reveal pathways between (1) working and living conditions; (2) working and living conditions and depression, as well as desesperación (desperation), the latter a Latino cultural idiom of distress frequently expressed by LMDLs; and (3) between living conditions and alcohol use. Discussion: Findings increase understanding regarding how challenging working and living conditions contribute to the same, as well as different, forms of psychological distress in LMDLs. Conclusions: Implications for mitigating structural vulnerability to psychological distress can be addressed at multiple social-ecological levels ranging from community-based support for enhancing LMDL employment (e.g., via day labor centers) to expanding the availability of work authorization for undocumented workers.