Urbanization presents significant challenges for Particularly Vulnerable Tribal Groups (PVTGs) globally, as it transforms landscapes and social structures, often undermining their traditional ecological knowledge and health practices crucial for their well-being. This study explores the complex interaction between urbanization, PVTG ecological knowledge, health, and overall well-being in evolving socio-environmental contexts. Through a review of existing literature and secondary data analysis, this study investigates the impact of urbanization on the ability of PVTG communities to uphold their traditional ecological knowledge systems and associated health customs, vital for their well-being. The study examines how urbanization disrupts traditional connections with the natural world, resulting in the depletion of medicinal plant resources, alterations in dietary habits, and changes in health behaviors among PVTG populations, thus impacting their overall well-being. Additionally, the study explores the socio-economic factors contributing to these changes, including market integration, infrastructural development, and cultural transformations. Despite these challenges, the study highlights instances of resilience and adaptation within PVTG communities as they endeavor to preserve ancestral wisdom while embracing contemporary realities to enhance their well-being. The findings underscore the pressing need for comprehensive development approaches recognizing the inherent value of PVTG ecological knowledge and its role in promoting community health, resilience, and overall well-being. Understanding the multifaceted impacts of urbanization on PVTG ecological knowledge, health, and well-being is crucial for policymakers and practitioners to devise inclusive and sustainable strategies that harmonize progress with tradition in rapidly urbanizing environments.