Purpose of Review <p>This review examines sex-based differences in prognosis and management of new-onset heart failure (HF), focusing on biological, clinical, and sociocultural determinants.</p> Recent Findings <p>Recent cohort studies and registries show that women with new-onset HF are older, more often present with HFpEF, and have lower early mortality but higher rehospitalization and worse quality of life. Men frequently present with HFrEF and ischemic etiology, experiencing higher short-term mortality. Emerging biomarkers, including galectin-3 and GDF-15, display sex-specific prognostic value. Persistent underrepresentation of women in clinical trials and disparities in access to guideline-directed therapy remain critical gaps.</p> Summary <p>Sex and gender substantially influence new-onset HF presentation and outcomes. Tailored diagnostic thresholds, sex-informed therapeutic strategies, and equitable research designs are essential to improve care. Future studies should integrate intersectional perspectives and precision medicine approaches to address disparities and optimize prognosis for all patients.</p>