The social determinants of health, and the structural inequities that influence them, create a disproportional effect on the health and well-being of people with low incomes and communities of color. Collaborations across organizations and sectors are important to address the social determinants of health. This brief explains how cross-sector partnerships can help; describes the significant role of locally embedded, data-driven organizations like the NNIP Partners; and provides examples of NNIP Partners that are already taking action on the social determinants of health.