Background: Clinical trials (CT) are important treatment options for patients with cancer, yet enrollment rates among underrepresented minority (URM) patients remain suboptimal. Oncology care teams need to assess barriers and facilitators of CT participation and identify practices and resources to better support patients. As part of a larger mixed-methods project, we elicited perspectives on improving URM CT enrollment from oncology research care teams and patients. Methods: We conducted four 60-minute focus groups with 12 oncology physicians, 12 research nurses, and nine clinical research coordinators, and semi-structured interviews with nine URM CT patients at a large academic medical center between January and December 2021. Results: Thematic analysis of the focus groups and interviews identified multiple barriers and potential resources and supports at the patient, healthcare team, institutional, and trial design levels. Barriers included difficulty ensuring patient understanding and informed consent, especially among patients with low health literacy and limited-English proficiency, complex logistical and financial demands of CT participation for patients, and the lack of multidisciplinary oncology care team collaboration. Collectively, these barriers undermined communication, trust, and the quality of patients’ relationships with the care team, all affecting CT participation. Suggested resources and practices included proactive needs assessments for all patients with early engagement of social workers, providing a liaison or navigator for each patient, services and support to reduce patient out of pocket costs, expansion of non-English materials availability and increased used of interpreters, increased training and diversity for all care team roles, and simplifying CT requirements by streamlining informed consent documents, eliminating unnecessary CT-related appointments, and broadening eligibility criteria. Conclusions: Findings suggest that changes in clinical trial design, care team coordination, and early assessment and monitoring of patients’ needs and experiences may help reduce access barriers and increase enrollment of URM patients into cancer CTs.