Background: The treatment landscape for la/mUC is evolving. Data on current real-world treatment trends in la/mUC are limited. This study assessed US physician treatment decision-making and prescribing patterns using qualitative interviews (QIs). Methods: First, a targeted literature search (TLS) evaluated published abstracts from January 2018 to March 2021. Then, in July 2021, QIs with 15 US medical oncologists/urologists were conducted based on the TLS findings. Physicians were recruited for a 60-minute, 1-on-1 phone interview. Physicians had to be in practice ≥1 year post fellowship, a board-certified oncologist/urologist, and managed ≥1 la/mUC patients who received first-line (1L) systemic therapy in the past 6 months. Results: Seven published US retrospective studies found relatively low utilization of 1L systemic therapy with 40%-65% of la/mUC patients not treated; high attrition rates reported with only 15%-40% of 1L patients receiving second-line (2L) therapy. The TLS included patient data collected primarily through 2017 and did not capture current systemic treatment patterns for recently approved therapies. QI respondents were community oncologists (n = 8), academic oncologists (n = 4), and community urologists (n = 3). The average number of la/mUC patients seen in the past 6 months was 23 per physician. Physicians estimated that ≥75% la/mUC patients are currently being treated with systemic therapy, with all oncologists prescribing 1L immunotherapy (IO) maintenance to eligible patients (n = 10 prescribing avelumab for ≥90%). According to 11 respondents (73%), the proportion of systemic-treated patients has increased in recent years with the availability of IO and novel therapies. Top reasons for not prescribing systemic therapy were poor performance status (73%), old age (67%), patient preference (53%), and comorbidities (47%). Physician-reported 1L regimens administered were 41% carboplatin-based, 37% cisplatin-based, 17% single-agent IO, and 4% nonplatinum chemotherapy. Top criteria impacting 1L regimen choice were renal function (100%), performance status (75%), neuropathy (75%), and age (50%). IO was typically reserved for patients who were platinum ineligible or refused chemotherapy. Ten oncologists reported that 60%-80% of 1L la/mUC patients received a 2L treatment. Conclusions: From the QIs, physicians reported higher treatment rates compared to the TLS; however, our physician sample was small, and the TLS included patient data through 2017 and thus did not capture current systemic treatment patterns. Findings suggest that, over time, the proportion of US la/mUC patients treated with/eligible for 1L systemic therapy has increased, including IO maintenance, as well as for subsequent lines due to increased treatment options after 2017. A quantitative survey of 150 medical oncologists is planned next for this study.