Colorectal cancer (CRC) remains a challenging disease due to its high diversity and complex immune escape mechanisms. The anticipated incidence of colorectal cancer is expected to reach 3,200,000 new cases per year, indicating a 63% increase, with an estimated 1,600,000 deaths occurring annually, which signifies a 73% rise by the year 2040. In contrast to current treatment modalities, such as chemotherapy, radiotherapy, and surgical interventions, immunotherapy has significantly enhanced both survival rates and overall well-being for patients diagnosed with CRC. One of the new immunotherapeutic options that shows promise in colorectal cancer treatment is immune checkpoint inhibitors (ICIs). By removing the immune system's inhibition, ICIs allow functioning cytotoxic T cells to identify and eradicate cancerous cells. The primary issue with checkpoint inhibition is the rise in autoimmune adverse events that limit treatment. In situ vaccination (ISV) also offers a promising strategy to enhance anti-tumour immunity by delivering tumour-specific antigens directly to the tumour microenvironment. In situ vaccination, facilitated by dendritic cells, promotes robust T-cell priming and memory formation within the tumour microenvironment. This review discusses the prospects of combining ISV with checkpoint inhibitors, which can enhance immune cell function. This dual approach may lead to a more potent and durable anti-tumour effect with minimal adverse events, ultimately contributing to significant improvements in tumour regression, overall survival, and the overall well-being of individuals diagnosed with CRC.