Abstract Tumor genomic testing and cancer clinical trials expand access to precision therapeutics, enhancing patient experience. However, physician and patient barriers impact participation of historically underrepresented patients (HUP), limiting generalizability for those most negatively affected by cancer. We interviewed patients to identify factors impacting genomic testing uptake and clinical trial enrollment. From 09/2021 - 12/2021 we interviewed 16 HUP diagnosed with cancer seen at an ambulatory oncology center: 3 spoke a language other than English, 9 identified as Black, 6 Hispanic/Latinx, 3 other race, and 3 older adult (age 70+). Individual interviews utilized a structured interview guide and lasted 45 minutes. Participants were recruited until thematic saturation was reached and transcripts were coded for major themes. Patients were unsure if they received genomic testing or if testing was recommended (citing possible confusion with medical information). Barriers included education (unclear benefit to participation, investigational drug/device identity, procedures involved), mistrust of research (data privacy concerns), and logistical accessibility (cost, time away from work, transportation). Those tested found it to be an easy process. Several cited that a patient advocate would be a beneficial resource to navigate the process. Barriers around clinical trial enrollment included education (risks of participating, size of the study, investigational drug/device identity), mistrust of research (data privacy, inclusion of HUP in trial, loss of autonomy in decision-making), and logistical accessibility (time commitment). HUP who participated in a trial appreciated additional psychosocial support and clinical monitoring. Patients were emphatically interested in genomic testing and cancer clinical trials when presented as the best course of care, though concerns about side effects from trials persisted. Patient barriers to genomic testing and clinical trials center around education, mistrust in research, and logistical accessibility. Patients who participated in genomic testing and clinical trials had a positive experience. Barriers may be addressed with tailored education, including supportive resources referral. Citation Format: Nadine J. McCleary. Barriers to genomic testing reduce clinical trial eligibility for diverse populations [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C070.