Background <p>Heart failure (HF) is associated with high morbidity, readmissions, and impaired quality of life. Because patient responses vary, tailored, nurse-led strategies, particularly in nutrition, activity, and psychosocial support, may address needs that routine care does not fully meet.</p> Objective <p>To assess the effectiveness of an individualized, nurse-led intervention integrating nutrition, graded exercise, and psychosocial support in patients with HF.</p> Methods <p>This prospective, single-center, parallel-group study involved adults with HF (<i>n</i> = 110 per group), who were assigned to groups using an odd-even allocation method. The control group (CG) received routine nursing care. The observation group (OG) received the same routine care plus a 3-month individualized program comprising customized nutritional counseling, staged exercise guidance, and structured psychosocial support with follow-up. Baseline and follow-up assessments consisted of measuring time to symptom resolution, cardiac function, arterial blood gases, nutritional status, psychological status, quality of life, and adverse events between the two groups.</p> Results <p>Compared with routine nursing care (CG), individualized nurse-led care (OG) had shortened time to symptom improvement (dyspnea 2.05 ± 0.61 vs. 2.57 ± 0.76 days; <i>p</i> &lt; 0.001), improved cardiac function (LVEF, CO ↑; LVEDD, LVESD ↓; 6MWT ↑; all <i>p</i> &lt; 0.05), enhanced gas exchange (PaCO₂ ↓, PaO₂ ↑; both <i>p</i> &lt; 0.05), and better nutritional status (<i>p</i> &lt; 0.05). Additionally, the OG had improved psychological status (<i>p</i> &lt; 0.05), enhanced quality of life (SF-36 75.43 ± 9.03 vs. 66.43 ± 9.09; <i>p</i> &lt; 0.05), and fewer adverse events (6.36% vs. 20.0%; χ²=7.462; <i>p</i> = 0.006).</p> Conclusion <p>An individualized nurse-led intervention is associated with multidomain benefits in patients with HF, supporting the integration of personalized nursing strategies into routine HF care pathways.</p>