Ubiquitous environmental occurrence of per- and polyfluoroalkyl substances (PFAS) underscores the critical need to broaden investigative efforts in effective screening, risk assessment, and remediation. Owing to the broad spectrum of PFAS, various analytical techniques have been extensively utilized to attain inclusivity, with notable attention given to methods such as extractable organic fluorine (EOF), adsorbable organic fluorine (AOF), and the total oxidizable precursor (TOP) assay. These techniques expand the scope of PFAS analysis by estimating perfluoroalkyl acid precursors or the total organochlorine fraction. This review offers a comprehensive comparative overview of up-to-date methodologies, alongside acknowledging the inherent limitations associated with their applications. When coupled with target analysis via low-resolution tandem mass spectrometry, these techniques offer a potential estimation of total PFAS concentrations. Yet, analytical challenges such as the limited availability of reference analytical standards, partial PFAS adsorption, and the entrapment of fluorinated inorganic anions on adsorbent materials often restrict the comprehensiveness of PFAS analysis. So, integrating nontarget analysis using high-resolution mass spectrometry (HRMS) tools fortifies these PFAS mass balance approaches, enabling the development of a more holistic approach for an environmental analysis framework. This review provides additional insights into the comparative advantages of PFAS analytical approaches and explores various data prioritization strategies in nontarget screening methods. It advocates for the necessary optimization of PFAS extraction methods, asserting that integrating the nontarget approach would foster the establishment of a comprehensive monitoring framework across diverse environmental matrices. Such integration holds promise for enhancing scientific comprehension of PFAS contamination across diverse environmental matrices.