System-wide investments generate health and enhance HIV, TB and malaria control in Malawi.

Global health initiatives have expanded access to HIV, tuberculosis, and malaria services in low-income countries, yet these programmes often operate within fragile health systems where shortages of healthcare workers and essential medicines limit their effectiveness and sustainability. Evaluating investments in health system capacity remains challenging because their benefits are difficult to attribute. Here, using a dynamic microsimulation model of Malawi's health system, we show that health system strengthening investments alone could avert 11.4% of disability-adjusted life years between 2025 and 2035, delivering a return of $26.1 per dollar invested. Combining system strengthening with HIV, tuberculosis, and malaria programme expansion produces three times greater health impact than disease-focused investment alone, delivering a return of $11.7 per dollar invested compared with $5.4 for disease-focused expansion alone. These findings support a shift toward integrated global health financing strategies that combine health system strengthening with disease-targeted programmes.