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Background: Precision health is a rapidly developing field, largely driven by the development of artificial intelligence (AI)–related solutions. AI facilitates complex analysis of numerous health data risk assessment, early detection of disease, and initiation of timely preventative health interventions that can be highly tailored to the individual. Despite such promise, ethical concerns arising from the rapid development and use of AI-related technologies have led to development of national and international frameworks to address responsible use of AI. Objective: We aimed to address research gaps and provide new knowledge regarding (1) examples of existing AI applications and what role they play regarding precision health, (2) what salient features can be used to categorize them, (3) what evidence exists for their effects on precision health outcomes, (4) how do these AI applications comply with established ethical and responsible framework, and (5) how these AI applications address equity and social determinants of health (SDOH). Methods: This protocol delineates a state-of-the-art literature review of novel AI-based applications in precision health. Published and unpublished studies were retrieved from 6 electronic databases. Articles included in this study were from the inception of the databases to January 2023. The review will encompass applications that use AI as a primary or supporting system or method when primarily applied for precision health purposes in human populations. It includes any geographical location or setting, including the internet, community-based, and acute or clinical settings, reporting clinical, behavioral, and psychosocial outcomes, including detection-, diagnosis-, promotion-, prevention-, management-, and treatment-related outcomes. Results: This is step 1 toward a full state-of-the-art literature review with data analyses, results, and discussion of findings, which will also be published. The anticipated consequences on equity from the perspective of SDOH will be analyzed. Keyword cluster relationships and analyses will be visualized to indicate which research foci are leading the development of the field and where research gaps exist. Results will be presented based on the data analysis plan that includes primary analyses, visualization of sources, and secondary analyses. Implications for future research and person-centered public health will be discussed. Conclusions: Results from the review will potentially guide the continued development of AI applications, future research in reducing the knowledge gaps, and improvement of practice related to precision health. New insights regarding examples of existing AI applications, their salient features, their role regarding precision health, and the existing evidence that exists for their effects on precision health outcomes will be demonstrated. Additionally, a demonstration of how existing AI applications address equity and SDOH and comply with established ethical and responsible frameworks will be provided.