Cardiovascular disease is the number one killer of females in the United States today, and myocardial infarction (MI) plays a role in many of these deaths. Females also present with more “atypical” symptoms than males and appear to have differences in pathophysiology underlying their MIs. Despite both differences in symptomology and pathophysiology being present in females versus males, a possible link between the two has not been studied extensively. In this systematic review, we analyzed studies examining differences in symptoms and pathophysiology of MI in females and males and evaluated possible links between the two. A search was performed for sex differences in MI in the databases PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature) Complete, Biomedical Reference Collection: Comprehensive, Jisc Library Hub Discover, and Web of Science. Seventy-four articles were ultimately included in this systematic review. Typical symptoms for both ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) such as chest, arm, or jaw pain were more common in both sexes, but females presented on average with more atypical symptoms such as nausea, vomiting, and shortness of breath. Females with MI also presented with more prodromal symptoms such as fatigue in days leading up to MI, had longer delays in presentation to the hospital after symptom onset, and were older with more comorbidities than males. Males on the other hand were more likely to have a silent or unrecognized MI, which concurs with their overall higher rate of MI. As they age, females have a decrease in antioxidative metabolites and worsened cardiac autonomic function than male. In addition, at all ages, females have less atherosclerotic burden than mles, have higher rates of MI not related to plaque rupture or erosion, and have increased microvasculature resistance when they have an MI. It has been proposed that this physiological difference is etiologic for the male-female difference in symptoms, but this has not been studied directly and is a promising area of future research. It is also possible that differences in pain tolerance between males and females may play a role in differing symptom recognition, but this has only been studied one time where females with higher pain thresholds were more likely to have unrecognized MI. Again, this is a promising area for future study for the early detection of MI. Finally, differences in symptoms for patients with different atherosclerotic burden and for patients with MI due to a cause other than plaque rupture or erosion has not been studied and are both promising avenues to improve detection and patient care in the future.