OBJECTIVES: Studies designed to assess the psychosocial factors affecting patients with mCRPC are sparse. Understanding this area may help patients and their caregivers communicate and make informed treatment decisions with their physicians. We used qualitative research methods to explore patient, caregiver, and physician experiences with oral oncolytic therapy.  METHODS: Our ecological approach postulates that patient, caregiver, and physician treatment decisions and experiences around mCRPC can result from multiple factors impacting individuals via social, organizational, community, governmental policy, and economic influences. Interview guides were developed and tested using core concepts of the ecological health model, and conducted with three relevant stakeholder groups: 30 patients with mCRPC, 26 caregivers, and an independent sample of 30 physicians (oncologists and urologists) who actively treat mCRPC. Patients and physicians were identified from a national claims database and caregivers were nominated by consented patients. Demographic information was collected on patients. Interviews were approved by an Independent Institutional Review Board. Interview responses were coded into QSR-NVIVO-10 software and analyzed using grounded theory. RESULTS: The majority of patients were age ≥70 years and Caucasian. Patients were taking either abiraterone acetate (32%) or enzalutamide (48%). Spouses were the predominant caregiver (89%). Physician specialty was stratified into oncologists (77%) and urologists (23%). Six major themes were identified: relationship with physicians; effects of disruptions to patients’ physical and social activities; communication with physicians; access to the medications; role of attitudes in coping with CRPC; and supports and communication. All stakeholders cited financial factors impacting access to treatment. CONCLUSIONS: There were different perspectives on the primary concerns around mCRPC, with patients citing loss of social functioning, caregivers fearing that patients would die, and physician citing pain. By improving understanding of these experiences, opportunities exist to improve treatment-related decisions for patients with mCRPC. These findings can also inform future quantitative population-based studies.