Background: While LuPSMA has a proven overall survival (OS) benefit in patients (pts) with mCRPC who have received prior taxane chemotherapy and androgen receptor pathway inhibitors, there is limited data on outcomes and efficacy of subsequent therapy in pts who have received LuPSMA. This study aimed to assess the clinical and treatment courses of pts with mCRPC after LuPSMA. Methods: We queried an IRB-approved prospectively maintained registry to evaluate all pts with mCRPC who received standard-of-care LuPSMA at our institution between June 2022 and July 2023. Clinical data pertaining to LuPSMA therapy as well as subsequent treatments were extracted from the medical record, including type and number of subsequent systemic therapies, reason for treatment cessation, hematologic support, and PSA response to subsequent therapy. PSA-50 was defined as a ≥50% decrease in PSA on therapy. Hematologic adverse events to therapies after LuPSMA were recorded and graded per CTCAEv5.0. Results: A total of 96 patients were evaluated; median age was 72 years (range 52-87), and median follow-up was 10 months. 18 pts completed all 6 cycles, 35 discontinued prior to cycle 6 of LuPSMA due to progressive disease, 10 died mid-treatment, and 33 were midway through treatment; median number of cycles received for all pts was 4 (range 1-6). None of the 18 who completed all 6 cycles had yet transitioned to a next line therapy. Of the 35 who discontinued LuPSMA, 17 transitioned to hospice due to disease progression, 15 initiated a subsequent line of therapy, and 3 had a treatment break. Median overall survival was 13 months in the entire cohort. Of the 15 receiving another line of therapy, 11 received cabazitaxel ± carboplatin/cisplatin, 1 received carboplatin with cisplatin substituted during carboplatin shortage, and 4 received other non-chemotherapy regimens; a PSA-50 response to subsequent therapy was seen in 4 patients (27%), all of whom received cabazitaxel ± carboplatin/cisplatin. Of the 12 pts who received chemotherapy, the median number of cycles received was 3 (range 1-7); 4 pts (33%) had grade ≥3 anemia, 2 (17%) had grade ≥3 thrombocytopenia and 7 pts (47%) required platelet growth factor support or transfusion of blood products. Conclusions: 47% of pts discontinuing LuPSMA transitioned to hospice due to disease progression while 44% proceeded to a subsequent line of therapy, the majority of whom received cabazitaxel. Outcomes to subsequent therapy were generally poor, with a 27% PSA-50 response rate. This initial experience may be biased by number of patients with limited standard of care options at the time of FDA approval of LuPSMA and could improve with better patient selection. However, this also highlights the continued need to develop novel therapeutic strategies for CRPC pts post-LuPSMA.