Social Determinants of Health (SDoH) are some of the most impacting factors affecting health today, accounting for up to 80% of modifiable health outcomes. This article explores 4 challenges faced by primary care providers in their efforts to screen and intervene patients with suboptimal SDoH: SDoH knowledge limitations; SDoH screening challenges; failure to integrate protective factors; and technical challenges when AI is used to assist with SDoH screening and intervention. Finally, we provide a broad overview of AI’s role in capturing and ameliorating deficient SDoH–all to reduce health disparities, improve health outcomes, help inform policymakers, and, foster thriving individuals and populations.