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The present study was motivated by the need to enhance indoor air quality and reduce airborne disease transmission in dense urban environments where high-rise residential buildings face challenges in achieving effective natural ventilation. The problem lies in the lack of scalable and convenient tools to optimize natural ventilation rate, particularly in urban settings with varying building heights. To address this, the scientific technique developed with an innovative metric, the urbanized natural ventilation effectiveness factor (uNVeF), integrates regression analysis of wind direction, velocity, air change rate per hour (ACH), window configurations, and building height to quantify ventilation efficiency. By employing a field measurement methodology, the measurements were conducted across 25 window-opening scenarios in a 13.9 m² residential unit on the 35/F of a Hong Kong public housing building, supplemented by the Hellman Exponential Law with a site-specific friction coefficient (0.2907, R² = 0.9232) to estimate the lower floor natural ventilation rate. The results confirm compliance with Hong Kong’s statutory 1.5 ACH requirement (Practice Note for Authorized Persons, Registered Structural Engineers, and Registered Geotechnical Engineers) and achieving a peak ACH at a uNVeF of 0.953 with 75% window opening. The results also revealed that lower floors can maintain 1.5 ACH with adjusted window configurations. Using the Wells–Riley model, the estimation results indicated significant airborne disease infection risk reductions of 96.1% at 35/F and 93.4% at 1/F compared to the 1.5 ACH baseline which demonstrates a strong correlation between ACH, uNVeF and infection risks. The uNVeF framework offers a practical approach to optimize natural ventilation and provides actionable guidelines, together with future research on the scope of validity to refine this technique for residents and developers. The implications in the building industry include setting up sustainable design standards, enhancing public health resilience, supporting policy frameworks for energy-efficient urban planning, and potentially driving innovation in high-rise residential construction and retrofitting globally. Full article