Background: Inequitable access to precision medicine limits its impact. To address disparities, we co-developed the Addressing Latinx Cancer Care Equity Study (NCT04843332), a multi-level intervention with community stakeholders. ALCANCE was designed for low-income and Latinx adults with cancer in rural Monterey County, California. We provided annual training for clinicians about testing guidelines and precision medicine disparities. Trained CHWs educated patients about precision medicine and encouraged them to raise the topic with their oncologist. We tested whether the intervention improved patient knowledge and receipt of precision medicine. Methods: Patients with newly diagnosed or recurrent cancer, age ≥ 18 years, able to consent in English or Spanish, and who self-identified as a racial and ethnic minority OR low-income status OR were insured by public or agricultural company insurance OR uninsured and receiving cancer care at Pacific Cancer Care, a rural community oncology practice in Monterey County, were randomized 1:1 to usual care (control group) or usual care augmented with the multi-level intervention for 12 months (intervention group). The primary outcome was whether the multilevel intervention could increase patient knowledge of precision medicine using a validated 6 question survey from time of enrollment (baseline) to 6-months post-enrollment between groups. A secondary outcome was receipt of precision medicine. CHWs and clinicians completed semi-structured interviews. Results: 110 participants were randomized; 70% (n = 67) reported Spanish as their primary language; 81% (n = 89) identified as Hispanic. Median age was 55 years (55.4 ± 14.3, mean± SD); majority had annual household incomes (USD) ≤ $34,999 (59.0%, n = 46); majority obtained a high school diploma/GED or less (67.3%, n = 74). Most had gastrointestinal (35.5%, n = 39) and breast (24.5%, n = 27) cancers and were diagnosed with stage 3 or 4 (64.5%, n = 71) disease. Precision medicine knowledge was low at baseline across both the control and intervention groups (23.5 ± 19.3 versus 23.0 ± 17.7, respectively). Intervention group participants had greater precision medicine knowledge at 6-months (39.2 ± 23.0) than control group participants (24.2 ± 20.0) with greater increase in knowledge overtime than control group participants (p < 0.001). More intervention group participants (n=46, 79.3%) received precision medicine testing than control (n=34, 60.7%). Across both groups, 26 of those tested had an actionable mutation. Of those 26, 66.7% (n=6 of 9) in the control group and 94.1% (n=16 of 17) in the intervention group received targeted therapy (p=0.065). Interviews with the care team indicated the model was acceptable and has been sustained as part of usual care. Conclusions: CHW-facilitated interventions may reduce disparities in precision medicine cancer care. Clinical trial information: NCT04843332