The introduction of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) has advanced perioperative systemic strategies, however, the roles of neoadjuvant and adjuvant therapy in locally advanced renal cell carcinoma (RCC) are still being explored. Phase II studies indicate that neoadjuvant therapy can reduce surgical complexity, but existing phase III trials have not confirmed reductions in recurrence risk or durable survival gains. In the adjuvant setting, only KEYNOTE-564 has established a one-year pembrolizumab regimen with an overall survival benefit, making it the sole guideline-endorsed strategy to date. The underperformance of multiple randomized controlled trials likely reflects suboptimal endpoint selection and limited sensitivity of assessment tools, along with variability in surgical quality and intrinsic tumor heterogeneity. Future research should focus on refined patient stratification, optimization of composite endpoints, and standardized surgical quality assurance, while integrating molecular subtypes and immune biomarker–based stratification within a multidisciplinary framework. Such efforts aim to build a personalized perioperative treatment paradigm, shift the field from empiricism to a biologically and evidence-driven model, and ultimately improve outcomes for locally advanced RCC.