Wastewater-based epidemiology (WBE) has emerged as a transformative approach for community-level health monitoring, particularly during the COVID-19 pandemic. This review critically examines the methodological framework of WBE systems through the following three core components: (1) sampling strategies that address spatial–temporal variability in wastewater systems, (2) comparative performance of different platforms in pathogen detection, and (3) predictive modeling integrating machine learning approaches. We systematically analyze how these components collectively overcome the limitations of conventional surveillance methods through early outbreak detection, asymptomatic case identification, and population-level trend monitoring. While highlighting technical breakthroughs in viral concentration methods and variant tracking through sequencing, the review also identifies persistent challenges, including data standardization, cost-effectiveness concerns in resource-limited settings, and ethical considerations in public health surveillance. Drawing insights from global implementation cases, we propose recommendations for optimizing each operational phase and discuss emerging applications beyond pandemic response. This review highlights WBE as an indispensable tool for modern public health, whose methodological refinements and cross-disciplinary integration are critical for transforming pandemic surveillance from reactive containment to proactive population health management.