The journey towards better healthcare sustainability in Asian nations demands a comprehensive investigation into the impact of urban governance, poverty, and female literacy on infant mortality rates. This study undertakes a rigorous exploration of these key factors to pave the way for evidence-based policy interventions, utilizing data from a panel of six selected Asian countries: Pakistan, China, India, Indonesia, Malaysia, and the Philippines, spanning the years 2001 to 2020. The findings reveal that adequate sanitation facilities, higher female literacy rates, and sustained economic growth contribute to a reduction in infant mortality. Conversely, increased poverty levels and limited women’s autonomy exacerbate the infant mortality rates observed in these countries. The Granger causality analysis validates the reciprocal relationship between urban sanitation (and poverty) and infant mortality rates. Furthermore, the study establishes a causal relationship where female literacy rates Granger-cause infant mortality rates, and conversely, infant mortality rates Granger-cause women’s autonomy in these countries. The variance decomposition analysis indicates that sustained economic growth, improved female literacy rates, and enhanced women’s empowerment will likely impact infant mortality rates in the coming decade. Consequently, in low-income regions where numerous children face potentially hazardous circumstances, it is imperative to allocate resources towards establishing and maintaining accessible fundamental knowledge regarding sanitation services, as this will aid in reducing infant mortality rates.