Background <p>Clinical practice guidelines strongly recommend oncology clinicians refer all advanced cancer patients for early intervention by a specialized palliative care (PC) team during treatment. Studies indicate that cancer patients receiving care in safety-net systems experience low rates of outpatient PC referral and delays in accessing care. Yet, few studies have examined factors influencing early PC implementation in settings predominantly serving underserved populations. This study qualitatively evaluated the multilevel (patient-, provider-, clinic-level) factors that influence early integration of PC for advanced cancer patients seen at a large, urban safety-net health system.</p> Methods <p>We conducted semi-structured interviews with medical oncology and PC clinic staff (attending physicians, fellows, advanced practice providers, registered nurses, administrators) who manage outpatient care for patients diagnosed with solid tumor cancers. The interview guide was informed by the Theoretical Domains Framework (TDF) to understand challenges, potential facilitators, and experiences with PC delivery. We analyzed interview transcripts using qualitative template analysis to identify salient themes.</p> Results <p>We interviewed 21 participants, including 17 clinicians (12 medical oncology, 5 PC) and 4 administrators. We identified nine barrier/facilitator subthemes spanning 10 of the 14 TDF domains and multiple levels of influence. <i>Patient-level</i>: (1) logistical and financial challenges (e.g., transportation, competing priorities), (2) lack of health literacy which oncology clinicians and PC nurses improve through education, (3) PC provides access to range of resources which positively impacts patient care (e.g., symptom management, care coordination). <i>Provider-level</i>: (4) lack of familiarity/awareness of clinical practice guidelines/institutional protocols for PC, (5) PC manages patient care for which oncology clinicians lack time or expertise, (6) oncology clinicians’ difficulty initiating PC conversations underscores communication is an essential skill. <i>Multiple levels</i>: (7) lack of appointment availability/limited clinic capacity, (8) patient appointment burden and synchronizing appointments, (9) multiple strategies can support PC integration (e.g., patient education materials, training for oncology clinicians/staff, and electronic health record alerts/reminders for PC referrals).</p> Conclusions <p>Our study findings suggest addressable challenges in implementing PC services for advanced cancer patients treated in a safety-net setting. The results will be used to inform development of a multilevel, multicomponent implementation strategy to improve early PC delivery and cancer outcomes for traditionally underserved patients.</p>