This review discusses the gender-specific genetic predisposition to breast cancer (BC), focusing on BRCA genes and other genetic factors. It highlights the differences in BC risk between men and women, emphasizing the importance of gender in BC management. While BC is commonly perceived as a female-only disease, it can also occur in men, albeit rarely, and in transgender individuals. Genetic risk factors play a significant role in BC predisposition, with BRCA1 and BRCA2 being the strongest genetic risk factors. BRCA1 is more commonly associated with female BC, while BRCA2 is more commonly associated with male BC. Other genes such as PALB2, CHEK2, and ATM also contribute to BC risk, with varying degrees of penetrance. The review also discusses the implications of these genetic factors for personalized clinical management, including risk assessment, screening, and treatment. It emphasizes the need for gender-specific approaches in BC management, as the genetic basis of male BC may differ from that of female BC. The review also addresses the challenges and open issues in establishing a gender-oriented clinical management for BC, including the need for more research on male BC and the importance of considering gender in genetic testing and treatment decisions. Overall, the review underscores the importance of considering gender in BC management to improve outcomes for both men and women.This review discusses the gender-specific genetic predisposition to breast cancer (BC), focusing on BRCA genes and other genetic factors. It highlights the differences in BC risk between men and women, emphasizing the importance of gender in BC management. While BC is commonly perceived as a female-only disease, it can also occur in men, albeit rarely, and in transgender individuals. Genetic risk factors play a significant role in BC predisposition, with BRCA1 and BRCA2 being the strongest genetic risk factors. BRCA1 is more commonly associated with female BC, while BRCA2 is more commonly associated with male BC. Other genes such as PALB2, CHEK2, and ATM also contribute to BC risk, with varying degrees of penetrance. The review also discusses the implications of these genetic factors for personalized clinical management, including risk assessment, screening, and treatment. It emphasizes the need for gender-specific approaches in BC management, as the genetic basis of male BC may differ from that of female BC. The review also addresses the challenges and open issues in establishing a gender-oriented clinical management for BC, including the need for more research on male BC and the importance of considering gender in genetic testing and treatment decisions. Overall, the review underscores the importance of considering gender in BC management to improve outcomes for both men and women.