The Yamuna River, vital for the sustenance of millions residing in Delhi, is heavily polluted with toxic heavy metals due to the effects of urbanization, industrialization, and untreated sewage discharge. Understanding the extent of heavy metal pollution and its associated health risks is crucial for effective environmental management. This study employs a comprehensive approach utilizing a modified Heavy Metal Pollution Index, Nemerrow Index, and health risk assessment to evaluate the pollution levels and potential health hazards in the Delhi stretch of the Yamuna River. Field observations, laboratory analyses, and statistical methods were employed during the research. Specifically, four sampling locations were selected, and 25 samples were collected from each site along a 22-km stretch in Delhi between March and June 2023. The findings reveal significant contamination of the Yamuna River in Delhi with heavy metals exceeding permissible limits set by regulatory bodies in Indian and International context. At the various sampling points, lead concentrations exhibited variability, with the highest concentration recorded at Wazirabad (2.332 mg/L) and the lowest at Okhla Barrage (1.092 mg/L). However, in terms of positive index (PI) and negative index (NI) values, Wazirabad registered the highest values of 2,639.97 and -0.02, respectively, while Okhla showed the lowest values of 31.21 for PI and -0.79 for NI. Conversely, at the Nizamuddin sampling site, the lowest PI and NI values were observed, standing at 31.21 and -0.79, respectively. Furthermore, the assessment of health risks related to heavy metal exposure involved metrics like the Hazard Quotient and carcinogenic risk models. The Total Hazard Index (THI) values ranged from 650 to 3,352 for infants, 341 to 1,843 for children, and 141 to 745 for adults. The THI values indicate that drinking water from the Yamuna River can result in various detrimental health conditions. This research enhances our understanding of the environmental health issues associated with heavy metal pollution in Delhi's Yamuna River. It underscores the importance of implementing holistic strategies for water quality management and pollution mitigation, stressing the integration of scientific assessments with policy actions and community engagement efforts.