Financial toxicity, including the burden of out-of-pocket expenses, can have a negative effect on patients’ decisions to seek medical treatment. Here, researchers looked at what influences a patient’s ability to pay for cutting-edge treatments for advanced prostate cancer. Men with advanced prostate cancer who were treated by commercial insurers between 2007 and 2019 were located using the OptumLabs Data Warehouse®. Treatment options for these patients included androgen deprivation monotherapy, new hormonal therapy, and nonandrogen systemic therapy. Patient financial responsibility for medical care in the first year of therapy was the major metric. Multivariate regression models were used to analyze the links between therapy and patient factors and out-of-pocket expenses. With the help of the Consumer Price Index CPI, all prices have been brought up to date with 2019 US dollars. The majority of the 13,409 males in the study group were treated with androgen deprivation monotherapy (n = 10,926), whereas just 6% (n = 832) were given new hormonal therapy, and 12% (n = 1,651) were given nonandrogen systemic therapy. Patients who chose androgen deprivation monotherapy spent an average of $165 on medical expenses in the first year, whereas those who opted for new hormonal therapy spent $4,236, and those who opted for nonandrogen systemic therapy spent $994. Nonandrogen systemic therapy and new hormonal therapy both had adjusted annual out-of-pocket expenses that were $752 (95% CI: $600-$903) and $2,581 (95% CI: $1,923-$3,240) greater than those of androgen deprivation monotherapy, respectively. Older age (65–74 years), Black race, lower comorbidity scores, and lower household income were also patient variables correlated (P<.05) with higher out-of-pocket costs related to therapy. Out-of-pocket expenses for patients with advanced prostate cancer who received new hormonal therapy were significantly greater. These findings highlight subgroups of patients who are particularly vulnerable to financial toxicity and encourage prescribers to consider it with other aspects of toxicity when discussing treatment options for advanced prostate cancer in the context of shared decision making.