Abstract: Colorectal cancer (CRC) is the most common malignant tumor of the digestive system worldwide. Because of the low early diagnosis rate of CRC, most patients are initially diagnosed in an advanced stage and have poor prognosis. Immune checkpoint inhibitors (ICIs) alone can only benefit some patients with MSI-H advanced CRC. Most patients are resistant to immunotherapy, and the mechanism of resistance may be associated with the lack of CD8⁺ T lymphocytes in the tumor microenvironment. Combined immunotherapy can eliminate the immune escape mechanism of tumors by inducing the enrichment and activation of CD8⁺T lymphocytes, upregulating PD-1/PD-L 1 activation, and reducing Treg cell proportions. To enable more patients to benefit from immunotherapy, including those with early CRC, and to evaluate the efficacy and prognosis of immunotherapy, new predictive markers, such as the tumor mutation burden, and immunoscore need to be assessed. This article reviews the interaction mechanism and recent progress of ICIs with oncolytic viruses in chemotherapy, radiotherapy, and targeted therapy for advanced CRC.