Cancer immunotherapy's remarkable success in treating previously intractable tumors comes with a sobering cardiovascular trade-off that disproportionately affects male patients. This reality challenges assumptions about equal treatment responses across sexes and demands personalized monitoring protocols for the millions receiving these breakthrough therapies. Analysis of adverse event data reveals that cardiovascular complications from immune checkpoint inhibitors carry a staggering 43.91% fatality rate, with over half occurring within the first month of treatment. Males consistently experience more severe cardiovascular toxicity than females when treated with these immune-activating drugs. Patients over 75 and those receiving anti-PD-1 therapies face elevated risk profiles. Single-cell RNA sequencing identified enhanced MIF and CD99 signaling pathways as potential molecular drivers of sex-specific cardiovascular damage. This finding represents a crucial advance in understanding why immunotherapy affects men's hearts more severely than women's. The cardiovascular risks are concentrated among lung and skin cancer patients, who comprise over 55% of affected individuals. These patterns suggest that current monitoring protocols may inadequately protect high-risk demographics. The research bridges a critical gap between clinical observation and molecular mechanism, offering concrete targets for intervention. For oncologists, these findings mandate sex-stratified risk assessment protocols and intensified cardiovascular monitoring for elderly male patients. The work also highlights an urgent need for cardio-protective strategies that could preserve immunotherapy's cancer-fighting benefits while mitigating life-threatening cardiovascular complications.