Per- and polyfluoroalkyl Substances (PFAS), also known as forever chemicals and ubiquitous persistence, pose significant public health challenges due to their potential toxicity, particularly in drinking water and soil contamination. However, PFAS occurrence and their concentrations in different environmental matrices vary globally, but factors influencing trends, transport, fate, toxicity, and interactions with co-contaminants remain largely unexplored. Therefore, this review critically examines the state-of-the-art worldwide PFAS sources, distribution, and pathways, and evaluates how PFASs are processed in wastewater treatment, generally, which causes severe problems with the quality and safety of drinking water. Importantly, the review also underscores health issues due to PFAS consumption and recent research trends on developing effective treatment strategies to manage PFAS contamination. Potential effects of PFAS were linked to urban land use and the proportion of wastewater effluent in streamflow. Besides, major emphasis was provided on challenges for conventional treatment, destructive technologies, environmental accumulation, precursor transformation, and cost-investment related to PFAS removal technologies. To combat PFAS contamination, this review proposes a framework that promotes the comprehensive identification of prevalent compounds, with a focus on their eradication through knowledge-based and targeted analysis. Additionally, it explores the ongoing debate surrounding PFAS laws and legal frameworks, offering ideas for enhancing contamination management. Lastly, this review provides a strategic plan for improving response and preparedness, serving as a foundation for addressing future environmental challenges and informing health risk assessments.