This review explores how polyunsaturated fatty acids (PUFAs), especially omega-3 types, interact with key inflammatory and immune pathways in colorectal cancer (CRC). By examining the molecular mechanisms behind PUFA action, the study sheds light on their potential to influence tumorigenic signaling, immune responses, and therapeutic outcomes. The authors suggest that understanding these interactions could guide the development of novel therapeutic targets and inform combinatory strategies involving PUFAs with immune checkpoint inhibitors or targeted therapies—marking an important step toward more precise and effective interventions for CRC.