Colorectal cancer (CRC) is reported as one of the most prevalent and deadliest malignancies globally, characterized by the formation of carcinogenic polyps over time. Genome complexity among CRC patients and clinical heterogeneity in tumors show variability in treatment response and disease management. Traditional medicinal approaches have fallen short in addressing this challenge. To overcome this problem, precision medicine has emerged as a promising alternative to patients for individualized care based on molecular profiling of each patient. To aid in more effective diagnosis and therapies, advancements such as next-generation sequencing and integration of artificial intelligence have enabled a major shift in disease monitoring and have significantly improved patient survival. This chapter explores the evolving role of precision medicine in diagnostics and therapy, while also highlighting the difficulties arising due to individual variability, tumor heterogeneity, and resistance mechanisms.