Greater understanding of the pathology of colorectal cancer has led to the integration of targeted treatment options. But not all targeted treatment options are the same, necessitating thoughtful selection of guideline-recommended therapy in collaboration with the patient. Stacey Cohen, MD, explores the significance of molecular profiling and tumor markers in personalizing immunotherapy for metastatic colorectal cancer. She also delves into the evolving landscape of targeted therapies, discussing the nuances and considerations of different options to optimize patient outcomes.