Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), known as the most detected per- and polyfluoroalkyl substances (PFAS) in various environmental compartments, have been associated with plastic pollution and endocrine dysfunction. Over the past 180 years (1839–2019), numerous emerging contaminants have been identified, with PFOA and PFOS receiving considerable attention based on scientific evidence and publications. Between 2018 and 2019, PFOA and PFOS experienced a relatively high increase rate of 18.8% and 13.6%, respectively. While developed countries have made progress in establishing stringent guidelines, developing and underdeveloped countries often lack regulations and mechanisms to address emerging PFAS. Furthermore, advancements in PFAS removal technologies are needed to improve their efficacy and feasibility. The establishment of regulatory compliances, along with exposure assessment and risk characterization, is essential for providing precautionary advice on water source protection, water supply security, health risks, treatment efficiency, and contamination forecasting. However, a more comprehensive approach and database for evaluating exposure and risks are still imperative to effectively combat PFAS contamination in drinking water. Therefore, this review aims to enhance environmental monitoring and management practices in response to the global crisis of PFAS contamination. The analysis of Needs, Approaches, Benefits, and Challenges (NABC) is grounded in the current trends of PFAS in the environment and human exposure through drinking water.