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Maternal mortality and morbidity in the United States remain substantially higher than in other high-income countries. Evidence suggests that exposure to chronic stress and social and environmental adversity contributes to maternal health risk through interconnected biological, psychological, and structural pathways. While these associations are documented, the molecular mechanisms linking adversity to maternal health outcomes remain poorly defined. This protocol describes a five-year, prospective, explanatory sequential mixed-methods cohort study (N = 200) designed to map how multilevel stress exposures influence biological and clinical outcomes among urban postpartum women. The study integrates geocoded neighborhood-level data, longitudinal electronic health records, and comprehensive interviewer-administered surveys assessing trauma, social support, and mental health. To identify the biological pathways of adversity, we employ multi-omics profiling of peripheral blood mononuclear cells-including DNA methylation, chromatin accessibility, and histone modification-alongside inflammatory and steroid hormone assays. Statistical frameworks, including Exposome-Wide Association Studies and spatial mediation modeling, will evaluate the interplay between socio-ecological stressors and molecular signatures during the postpartum period. Findings will advance understanding of the biological embedding of adversity and inform multilevel interventions to improve maternal health outcomes.