Background: Recruitment of cancer patients into clinical trials (CTs) is a challenge. We aimed to explore how patient eligibility assessment is conducted in practice, what factors support or hinder this process, and to assess the potential usefulness of Clinical Trial Recruitment Support Systems (CTRSS) for patient-to-trial matching. Methods: We conducted semi-structured interviews in France with healthcare professionals involved in cancer CTs and experts on trial recruitment. We focused on the stages in-between trial feasibility, and patient information and consent. Interviews were recorded, and the transcripts were analyzed thematically. We used the Systems Engineering Initiative for Patient Safety (SEIPS) 2.0 framework to organize our results. Results: We interviewed 25 participants. We identified common steps for cancer patient eligibility assessment: prescreening under medical supervision, followed by the validation of patient-trial matching based on manual chart review. This process built on rich interactions between clinicians, other professionals (clinical research assistants, data scientists, medical coding experts), and patients. Technological factors, mainly related to data infrastructure (both for patient data and trial data), and organizational factors (research culture, incentives, formal and informal research networks) mediated the performance of the recruitment process. Participants had mixed feelings towards CTRSSs; they welcomed automated pre-screening but insisted on manual verification. Given the necessary collaborative nature of multisite trials, coordinated efforts to support a common data infrastructure could be helpful. Conclusions: Material, organizational, and human factors affect cancer patient eligibility assessment for CTs. Patient-to-trial matching tools bear potential, but good understanding of the ecosystem, including stakeholders' motivations, is a prerequisite.