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This study integrated Geronimus’ weathering, the conceptual understanding of social disadvantage’s wear-and-tear effects on physiological stress response and chronic diseases, to investigate the relationship between social determinants of health (SDoH), allostatic load (AL), and type 2 diabetes and cancer outcomes. We conducted a secondary analysis of survey and electronic health data of a diverse U.S. Latina sample from the All of Us Research Program. Out of 6,639 participants, 35.2% were diagnosed with type 2 diabetes and 21.3% with at least one type of cancer. Both conditions shared risk factors such as age, Mexican heritage, low SES, and food insecurity. Being U.S.-born, low-SES, and living in the Midwest were risk factors for elevated AL. Lastly, AL predicted diagnosis odds for type 2 diabetes but not cancer and did not mediate the association between SDoH and disease diagnoses.