This chapter examines the complex interplay between urbanization, industrialization, public health, and climate change in shaping the sustainability of Indonesia’s delta regions. Rapid urban expansion, particularly in Java Island, has led to uncontrolled sprawl, disrupting spatial planning and increasing flood risks due to the loss of natural water absorption areas. The delta region, as one of the important natural resources, has suffered significant degradation, partly due to extensive industrial activities. Several areas in the provinces of Central Kalimantan, Riau, and Southeast Sulawesi, which serve as mining zones and have fostered urban growth around industrial sites, are also facing environmental challenges particularly the limited access to clean water and sanitation, which poses potential health risks. Industrial growth has intensified environmental degradation, contributing to rising carbon emissions, pollution, and inefficient waste management. These challenges, exacerbated by climate change, threaten ecological balance and heighten public health risks, including waterborne diseases and bacterial infections. To address these complexities, a multidisciplinary approach is essential. Integrated adaptive urban strategies and community-based solutions such as constructed wetlands and sustainable waste management play a crucial role in enhancing resilience. A holistic framework that combines environmental governance, public health initiatives, and climate adaptation measures is key to ensuring the long-term sustainability of Indonesia’s delta regions amid ongoing environmental and socio-economic transformations.