Our knowledge of PFAS fate and transport in the urban water cycle between water treatment plants (WTPs) and wastewater treatment plants (WWTPs) is dependent upon analytical methodology. To conduct a mass balance of PFAS through these engineered systems, environmental analytical chemistry must be leveraged to quantify PFAS in the various media that cycle through these facilities. Although mass balances have been attempted across various unit treatment processes for a small selection of PFAS in WTPs and WWTPs, system-wide mass balances are a daunting challenge that have not been achieved to date. The continued existence of legacy PFAS and the constantly moving target of newly emerging commercial PFAS and transformation products (TPs), in addition to complications resulting from bias-free collection of uncontaminated samples for PFAS in the parts-per-trillion (ppt) range, complicate a mass balance. Further compounding a mass balance is the diverse universe of PFAS which consists of polar/nonpolar, nonvolatile/semi-volatile/volatile, and neutral/anionic/cationic/zwitterionic chemicals. The physicochemical properties of these chemicals, and the media in which they exist, drive the selection of appropriate analytical procedures to provide accurate and precise quantification of these compounds. The current state of analytical science for PFAS is development of methods specific for subgroups of PFAS families in limited matrices. Here, approaches to integrate analytical workflows across types of PFAS and media are proposed. In this evaluation, multi-platform targeted, suspect/non-targeted, and surrogate screening methods combining promulgated standardized methods and emerging procedures are presented. Synthesis of a comprehensive analytical workflow that aspires to achieve a mass balance of PFAS across the gaseous, solid, and aqueous matrices encountered in WTPs and WWTPs is proposed. Finally, research data gaps and future research needs are also discussed.