Purpose <p>This study explored perspectives on clinical trial-related financial considerations from patients with breast cancer receiving treatment in the Deep South who declined trial participation.</p> Methods <p>This qualitative content analysis included interview data from patients offered participation in a breast cancer clinical trial yet declined to participate from July 2020 to January 2024. Semi-structured interviews elucidated the influence of financial factors in the decision to decline enrollment onto a trial. Open coding was used to develop the codebook via an inductive approach to identify key concepts, patterns, and themes from the transcribed interviews. Transcribed interviews were then coded deductively by two independent reviewers.</p> Results <p>Of 21 patients with breast cancer, 43% and 57% previously declined participation in a therapeutic and non-therapeutic clinical trial. Interviews revealed four themes related to the influence of financial factors in the decision to decline participation in clinical trials, including (1) trial participation expenses (e.g., direct and indirect participation expenses), (2) insurance coverage (e.g., barriers for insured, resource for uninsured), (3) socioeconomic status (inequities and trust in clinical trials), and (4) financial compensation for trial participation (e.g., facilitating participation, inappropriate incentivizing).</p> Conclusion <p>Future interventions targeting financial barriers to trial participation for patients most vulnerable to experiencing financial disparities are needed to diversify cancer clinical trial participation, thus ensuring results are generalizable to all patients.</p>