Contemporary psychiatry has undergone a paradigm shift, recognizing gender as a critical determinant of mental health beyond biological reductionism. This analysis explores how gender interacts with neurobiological, psychological, and sociocultural factors, shaping epidemiological disparities, diagnostic biases, and therapeutic inequalities. Epidemiological data reveal significant gender differences: depressive disorders show a female predominance (1.7:1 in Western countries, rising to 2.3:1 in low-income settings), while substance use disorders are more prevalent in men (2.8:1 globally). Neurobiological studies highlight sex-based variations in stress response (e.g., prolonged HPA axis activation in women) and drug metabolism (e.g., slower CYP450 activity increasing adverse effects). Psychosocial factors—such as caregiving burdens (73% borne by women) and hegemonic masculinity norms—further exacerbate mental health disparities. Diagnostic biases persist, with women overdiagnosed with depression (73% vs. 62% of men with similar symptoms) and men underdiagnosed for internalizing disorders. Pharmacological disparities include women receiving 1.8 times more benzodiazepines and facing higher polypharmacy risks, while men are prescribed higher antipsychotic doses. Intersectional analyses underscore compounded risks for marginalized groups (e.g., migrant women’s elevated depression rates). Proposed reforms include gender-sensitive medical training, SGBA (Sex and Gender-Based Analysis) in research, and AI-driven clinical alerts to mitigate biases. Achieving equity requires addressing structural determinants and implicit biases in mental health care.