Background: Cancer care delivery has been described as a “system in crisis” in part due to lack of affordable care. In 2019, out-of-pocket (OOP) costs alone were estimated to be over $16 billion in the US. Transparency and early conversations about expected OOP costs may prevent financial toxicity and improve patient-centered care. Methods: We conducted a qualitative study to explore perceptions of OOP costs and technology use to promote cost transparency. Semi-structured, in-depth interviews were held with various healthcare professionals (HCPs) – including oncologists, nurse patient navigators, financial counselors, social workers, and pharmacists – and patients enrolled in fee-for-service Medicare receiving cancer drug therapy at a large, urban cancer center or affiliated community practice. HCPs were asked about common issues patients have regarding cancer treatment costs and how they search for patient financing opportunities. Patients were asked about difficulty with treatment costs not covered by insurance, conversations with care team members about how much they should expect to pay for treatment, and how they learned about their OOP costs. All interviews were led by a health economist/policy expert and a qualitative research assistant between October 2020 and June 2021. Results: We interviewed 13 HCPs and 3 patients. HCPs averaged 16 years of experience working with cancer patients (range: 1-39 years). Patients were ≥50 years old and had at least a high school degree or the equivalent. We identified at least 10 roles that may be involved in discussing or identifying resources to lower expected OOP costs (i.e., cost navigation) for cancer patients receiving systemic infused or oral treatments. OOP treatment costs were identified as a top concern for patients and HCPs, echoing known challenges; however, how OOP costs are determined and navigated varies tremendously per patient. Emergent themes in the data include: lack of transparency in OOP costs and the navigation process, a need for cost conversations at the start of treatment, challenges with obtaining financial assistance, and numerous barriers impeding cost navigation. There are opportunities for technology to streamline support for navigation tasks. Conclusions: Helping patients understand and seek assistance to cover high OOP costs is critical for many patients with high-priced cancer treatments. However, it is a complex process that often requires engagement from multiple care team members who may encounter barriers to providing this help. Patients who cannot afford their OOP costs may benefit greatly from close partnership with an HCP who assists with navigation throughout the process. Technology is needed to support a variety of backend tasks to help HCPs determine expected OOP costs and maintain the focus of the oncologist’s role – to provide the patient with the best possible treatment.