RAS-related signaling system plays an important role in the occurrence and development of colorectal cancer, which is closely related to the proliferation, metastatic potential, and apoptosis of colorectal cancer cells. However, treating this type of cancer with a single medicine, either targeted therapies or chemotherapies, is not always the best option. In recent years, RAS-related signaling pathway inhibitors have been utilized in conjunction with other medications with promising outcomes in clinical trials and preclinical investigations. When used in concert with other anti-cancer drugs, EGFR inhibitors, VEGF inhibitors, RAS direct inhibitors, MEK inhibitors, and RAF inhibitors have shown particularly impressive performance. In terms of clinical value, combining cetuximab with chemotherapy regimens, EGFR inhibitors with chemotherapy regimens, and EGFR inhibitors with other anti-cancer drugs dramatically enhanced important indicators in patients with colorectal cancer who had wild-type RAS. However, treatment options for patients with RAS-mutant colorectal cancer have been less favorable, and in this context, anti-angiogenic and anti-EGFR agents and immune checkpoint inhibitors have been approved as second-line treatment options. In preclinical studies, inhibitors that directly target RAS have been shown to be effective in combination with other drugs, and other treatment options have also shown good results, giving patients with colorectal cancer unlimited hope. This review focuses on the relationship between RAS-related signaling pathways and colorectal cancer, combination tactics in clinical trials and preclinical studies, and research on drug resistance mechanisms linked with composition administration in order to lay the foundation for future clinical multidrug therapy strategies.