Background/Objectives: Frailty is well-recognized as a predictor of adverse postoperative outcomes. The Clinical Frailty Scale (CFS) is a widely recommended frailty assessment tool due to its simplicity and rapid bedside applicability; however, it has never been validated in Serbia. The aim of this study was to translate, culturally adapt, and validate the CFS in Serbia, in patients undergoing elective major surgical procedures. Methods: This cross-sectional study included 149 patients aged ≥50 years undergoing elective major urological oncology surgery. Frailty was assessed preoperatively using three scales: the CFS, the Edmonton Frail Scale (EFS), and the FRAIL scale. The CFS evaluations were independently performed by two raters and repeated after 7 days. Concurrent validity was evaluated via Spearman’s correlation between the CFS, the EFS, and the FRAIL scale. The “known-group” construct validity of the CFS was assessed using the test for trends across clinically relevant groups. Both inter-rater and test–retest reliability were assessed using the intraclass correlation coefficient (ICC). Results: The CFS was translated and culturally adapted into the Serbian language in accordance with ISPOR guidelines. The Serbian version of the CFS demonstrated both excellent inter-rater reliability (ICC = 0.957; 95% CI 0.941–0.968), and test–retest reliability (ICC = 0.958; 95% CI 0.943–0.970). A strong positive correlation was observed between the CFS and both the EFS (ρ = 0.698) and the FRAIL scale (ρ = 0.614). A known-group comparison confirmed the construct validity of the CFS. Conclusions: The Serbian version of the CFS is a reliable, valid, and clinically feasible tool for preoperative identification of frailty in patients aged 50 years and older undergoing major elective uro-oncological procedures.