Colorectal cancer is a major global health concern, necessitating the identification of biomarkers for early detection, prognosis, and therapeutic targeting. In recent years, proteomic and genomic approaches have revolutionized cancer research, providing valuable insights into the molecular mechanisms underlying CRC. Epidemiological and clinical studies point to a connection between inflammation and development of cancer. Incidences of (CRC) have increased globally during the past decade. In this review, we will discuss the biomarker discovery approach for CRC, which involves a combination of proteomic and genomic perspectives. There are numerous promising biomarkers that must improve life expectancy or quality of life to be evaluated for use in clinical practice. We will cover the important steps such as sample collection, protein extraction, separation, mass spectrometry (MS) analysis, genomic profiling, data analysis, validation, and functional characterization. By utilizing both proteomics and genomics, researchers can identify potential biomarkers for CRC, leading to better diagnostics and personalized treatment options.