As generalized treatments struggle to control colorectal cancer (CRC), global cancer incidence and overall death rates rank fourth and fifth, respectively. Personalized medicine is becoming increasingly popular. Heterogeneity in colorectal cancer often leads to failure and ineffectiveness of surgery, chemotherapy, and radiation therapy in almost all cases. A variety of genetic and epigenetic variables contribute to CRC heterogeneity, attributing to difficulties in treatment response and causing drug resistance. Additionally, genomic expressions and their interaction with the living niche may elicit distinct responses and molecular features in tumours, comparable with histological characteristics. Thus, in order to assist the selection of the most effective treatment strategy, the patient’s personal medical history, genomic profiles, and biomarkers related to the procedure are all taken into account in personalized medicine. By analysing the patient’s genetic transcriptome and epigenetic characteristics, personalized medicine determines the most effective course of treatment and diagnostic procedures on the basis of how particular genetic variants are addressed by the targeted medicines. Immunotherapy, phytochemicals, and other biomarker-specific targeted medicines are among the tailored approaches being investigated for the treatment of colon cancer. However, there are several obstacles that need to be addressed to fully incorporate personalized medicine into the healthcare system. This chapter aims to compile all relevant and current data on colon cancer that pertains to personalized treatment.