Background: Cancer mortality has declined over the past decade due to clinical advances including precision medicine. Despite these clinical advancements, low-income and racial/ethnic minorities experience worse cancer morbidity and mortality. Specifically, these populations have lower rates of genomic testing and are significantly underrepresented in precision medicine research. Community-based, culturally tailored approaches are needed to address these ongoing disparities. The objective of this randomized controlled trial is to test whether a community health worker (CHW)-led intervention can improve patient understanding of precision medicine topics and delivery of evidence-based cancer care more than usual cancer care alone. Methods: We developed a county-wide cancer care initiative and a community advisory board (CAB) comprised of patient, caregiver, payer, clinician, and governmental stakeholders in Monterey County—comprised of 60% Latinx, non-English speaking, immigrant populations. As guided by the CAB, we developed a CHW-model to provide education on precision medicine and screen for complications of social determinants of health in 1:1 discussions with patients. In collaboration with a local community oncology clinic, we plan to randomize 110 patients with cancer who are receiving active treatment into usual care or usual care plus the CHW-led intervention. Inclusion criteria includes patients who are: 1) 18 years of age or older; 2) racial/ethnic minorities; 3) low-income; 4) uninsured or insured by Medicaid and/or local agricultural employers; and 5) speak English or Spanish. Exclusion criteria includes: 1) lack capacity to consent to study procedures; 2) plan to move from the area within a year. We will measure the effect of the intervention on patient knowledge of precision medicine using a survey adapted from Davies et al. Secondary outcomes include effect on health-related quality of life using the Functional Assessment of Cancer Therapy – General, patient activation using the Patient Activation Measure, satisfaction using the Satisfaction with Decision Scale, prognosis and treatment preferences using an adapted survey by Weeks et al., healthcare utilization, and receipt of evidence-based cancer care. We will administer surveys at baseline, 3-, 6- and 12-months post-enrollment. To date, 67 participants have been enrolled. This study will show if CHW-models increase knowledge of precision medicine in this population. Clinical trial information: NCT04843332.