This systematic review and meta-analysis investigated the association between saturated fatty acids (SFAs) and cancer risk. The study analyzed 55 studies, including 38 case-control studies and 17 cohort studies, published up to December 2023. The results showed a significant positive correlation between elevated levels of total SFAs and cancer risk, with an odds ratio (OR) of 1.294 (95% CI: 1.182–1.416; P < 0.001). Specific SFAs, such as C14:0, C16:0, and C18:0, were also associated with increased cancer risk. However, no significant association was found for other SFAs like C4:0, C6:0, C8:0, C10:0, C12:0, C20:0, C22:0, and C24:0. Subgroup analyses revealed that excessive dietary SFA intake and elevated blood SFA levels were linked to higher cancer risk, particularly for breast, prostate, and colorectal cancers. The study also found no significant association between SFA levels and lung, pancreatic, ovarian, or stomach cancers. The findings suggest that high total SFA levels may increase cancer risk, and specific SFA subtypes may contribute to this risk. The study highlights the need for further high-quality research to confirm these associations and to develop dietary strategies for cancer prevention. The results could inform clinical trials combining diet-related interventions with immunotherapy to improve cancer outcomes.This systematic review and meta-analysis investigated the association between saturated fatty acids (SFAs) and cancer risk. The study analyzed 55 studies, including 38 case-control studies and 17 cohort studies, published up to December 2023. The results showed a significant positive correlation between elevated levels of total SFAs and cancer risk, with an odds ratio (OR) of 1.294 (95% CI: 1.182–1.416; P < 0.001). Specific SFAs, such as C14:0, C16:0, and C18:0, were also associated with increased cancer risk. However, no significant association was found for other SFAs like C4:0, C6:0, C8:0, C10:0, C12:0, C20:0, C22:0, and C24:0. Subgroup analyses revealed that excessive dietary SFA intake and elevated blood SFA levels were linked to higher cancer risk, particularly for breast, prostate, and colorectal cancers. The study also found no significant association between SFA levels and lung, pancreatic, ovarian, or stomach cancers. The findings suggest that high total SFA levels may increase cancer risk, and specific SFA subtypes may contribute to this risk. The study highlights the need for further high-quality research to confirm these associations and to develop dietary strategies for cancer prevention. The results could inform clinical trials combining diet-related interventions with immunotherapy to improve cancer outcomes.