<p>Gastrointestinal (GI) cancers remain a leading cause for global cancer-related morbidity and mortality, affecting both—men and women. Recent research highlights significant differences between the sexes in terms of incidence, development and treatment outcomes. The interplay between genetic, environmental, diet and lifestyle, and hormonal factors such as estrogen, progesterone and androgens forms a pivotal axis influencing various GI cancer development and therapeutic responses. Women’s unique vulnerability and resilience to GI cancers are influenced by differences in immune response, genetic profiles and exposure to risk factors. Site-specific evaluations show that hormonal factors can either protect or predispose women to certain cancers, often depending on life stage and hormonal status. Gender-directed approaches to prevention, screening and treatment, along with tackling psycho-social burdens and detection challenges, will significantly impact the outcomes of GI cancer in women. Further research in this area is vital to enhance outcomes and address gaps in GI cancer care for women.</p>