Background: Combination therapy based on immunotherapy (IO) alone or in combination with oral tyrosine kinase inhibitors (TKI) has become the standard of frontline therapy in metastatic renal cell carcinoma (RCC). We sought to ascertain real world data on financial implications in RCC patients on combination therapy. Methods: An online survey was administered by Kidney Cancer Research Alliance (KCCure), a non-profit patient advocacy group, between 07/2022 and 09/2022 to patients via website, mailing lists and social media platforms. Multiple responses from the same patient were prohibited via anonymized IP address tracking. Select questions were directed at questions related to financial concerns as well as the validated 11-item COST measure and out-of-pocket spending patterns related to supplement purchases. Pearson’s correlation (r) and Kendal’s tau test were used to analyze the COST questionnaire, financial burden and hardship. Significance levels were 2 tailed. Results: 289 responders were on combination therapy (IO+IO or IO+TKI) (M:F, 145:143). Median age was 61 (range 19-89). 177 pts answered the COST questionnaire. Patients identified themselves as white (91%), living in the US (86.8%) and had a bachelor's degree or beyond (52.9%). 21.1%, 46.1%, and 32.6% lived in urban, suburban, and rural locations. The approximate annual household income was <50.000US$ in 17%, <100,000US$ in 41% and >200,000US$ in 15%. 61% had private insurance, 27% were on Medicare/Medicaid and 0.6% were uninsured. 14% reported that it was difficult or very difficult to pay their premiums. 31% were retired and 24% not able to work. 28% reported that their medical situation has not reduced their income at all and 26% claimed that their disease reduced their income very much. Significant financial, medical, behavioral, psychological and emotional hardship was reported by 15%, 26%, 12%, 19% and 24% of the patients respectively. The monthly out of pocket costs were independent of type of therapy with 50% of the patients reporting spendings of <50US$. 36% reported high out of pocket costs are a barrier to care. 44% have received financial support through a manufacturer or a foundation.22.4% of responders reported spending >$100/month on supplements, and 8.3% reported spending >$250/mo. Median COST score was 22 (range 4-36). COST score was significantly correlated to age, NCCN distress score, time since diagnosis and supplement intake (p<0.05). Conclusions: Systemic therapy imposes financial hardship on patients but does not seem to be worse with combination therapy in RCC. Route of administration is not influencing financial hardship. Patients are willing to pay for out supplements if their treatment is not causing financial harm.