<p>Sex is a critical determining factor in cancer incidence, pathogenesis, and outcome. These effects result from sexual differentiation influencing mechanisms that regulate both normal and cancer biology. Iron biology is sexually dimorphic in nature and plays a key role in tumorigenesis. Therefore, iron metabolism may be a key driver of sex-biased differences in cancer. In this article, we review and synthesize the existing literature examining iron’s role in driving sex differences in tumor incidence, progression, response to therapy, and overall survival in different cancer types. We also explore models that could be useful in studying iron metabolism–driven sex differences in tumorigenesis.</p>