Water treatment systems are indispensable components of modern infrastructure, and play a crucial role in public health. However, current understanding of the mixture toxicity in both untreated and treated water, especially regarding disinfection byproducts (DBPs), is limited. Additionally, there is a lack of discussion on upgrading wastewater treatment plants (WWTPs) to strategically balance the economic, environmental, and social needs of municipalities. This work aims to bridge these knowledge gaps by delving into the chemical, toxicological, and energy/resource recovery dimensions of water treatment systems. The first study focuses on the characterization of water toxicity in raw and treated drinking water from various plants across the United States. It examines toxicity levels pre- and post-disinfection, linking specific DBPs to health effects while proposing a biomarker-based approach for toxicity evaluation. It emphasizes the prominence of certain DBP classes, and provides insights for monitoring and risk assessment in drinking water. The second study explores the impact of diverse disinfection technologies on reclaimed water toxicity, employing toxicogenomics assays and chemical analysis to evaluate eight disinfection methods. It highlights the effectiveness of chlorination and ozonation in reducing overall toxicity, contrasting with chloramination, and underscores the importance of considering DBPs and other undetected chemicals in toxicity evaluation. This study provides a comprehensive toxicogenomic analysis, revealing distinct toxicity profiles influenced by various disinfection processes. The third study centers on transforming traditional WWTPs into energy-positive water resource recovery facilities, with New York State as a case study. It proposes a decision tool to optimize retrofit designs for individual WWTPs, considering factors like maximizing net present value, minimizing levelized cost of energy, reducing greenhouse gas emissions, and minimizing life-cycle environmental damage. The study recommends integrating food waste co-digestion and innovative energy recovery technologies, and identifies specific WWTPs for strategic retrofitting based on economic, environmental, and social considerations. In summary, these studies collectively highlight the critical aspects of public health and circular economy, and provide insights for future monitoring and management strategies in water treatment systems.