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A recent National Academies report recommended that health systems invest in new infrastructure to integrate social and medical care. Although many health systems routinely screen patients for social concerns, few health systems achieve the recommended model of integration. In this critical case study in an urban safety net health system, we describe the human capital, operational redesign, and financial investment needed to implement the National Academy recommendations. Using data from this case study, we estimate that other health systems seeking to build and maintain this infrastructure would need to invest $1 million to $3 million per year. While health systems with robust existing resources may be able to bootstrap short-term funding to initiate this work, we conclude that long-term investments by insurers and other payers will be necessary for most health systems to achieve the recommended integration of medical and social care. Researchers seeking to test whether integrating social and medical care leads to better patient and population outcomes require access to health systems and communities who have already invested in this model infrastructure. (Am J Public Health. 2024;114(6):619–625. https://doi.org/10.2105/AJPH.2024.307602) [ABSTRACT FROM AUTHOR]