Despite significant advancements in targeted- and immunotherapies, millions of patients with cancer still succumb to the disease each year. In renal cell carcinoma, up to 25% of metastatic patients do not respond to first-line therapies. This reality underscores the urgent need for innovative or repurposed therapies to effectively treat these patients. Patient-derived organoids represent a promising model for evaluating treatment efficacy and toxicity, offering a potential breakthrough in personalized medicine. However, utilizing organoid models for drug screening presents several challenges. Our protocol aims to address these obstacles by outlining a practical approach to successfully isolate and cultivate patient-derived renal cell carcinoma and kidney organoids for treatment screening purposes.