Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. While conventional cancer therapies like chemotherapy and radiation can be effective, they often have significant side effects and limited efficacy. Emerging evidence suggests that modulating the gut microbiome through probiotics and postbiotics may offer a promising complementary approach for CRC treatment and prevention. Probiotics are live microorganisms that, when administered in adequate amounts, can confer health benefits to the host. Postbiotics are the bioactive compounds secreted by probiotic bacteria, including metabolites, cell wall components, and extracellular vesicles. These probiotic-derived compounds have demonstrated potent anti-inflammatory, antiproliferative, and immunomodulatory properties that can target various hallmarks of cancer. Furthermore, nanotechnology has the potential to enhance the delivery and efficacy of probiotics and postbiotics for CRC treatment. Nanoparticle-based systems can improve the stability, bioavailability, and targeted delivery of these bioactive compounds, leading to more effective modulation of the gut microbiome and its interactions with the host. This book chapter will provide a comprehensive overview of the integration of probiotics, postbiotics, and nanotechnology for enhanced treatment efficacy in CRC. It will discuss the role of gut microbiome dysbiosis in CRC development, the mechanisms of action of probiotic-derived bioactive compounds, the application of nanotechnology to improve the delivery of probiotics and postbiotics, preclinical and clinical evidence on the synergistic effects of these integrated strategies, and challenges and future perspectives in the development of innovative CRC treatment approaches.