Biological exposure assessments are invaluable for objectively determining exposure to environmental pollutants within a population and identifying the factors driving that exposure, with the aim of proposing solutions to reduce it accordingly, as part of a preventive and decision-support approach. Conducting exposure studies can be useful for providing concrete answers to local pollution situations: Are residents exposed to the pollutants in question? Are they exposed to a greater extent than the general population? What are the sources of exposure that could explain the exposure levels? Is it possible to draw conclusions regarding the health risks to residents resulting from exposure to this pollution? However, exposure studies face several challenges: high cost, a complex logistics chain, the feasibility of measuring relevant biomarkers (availability of biomarker-matrix pairs), a limited study area, a small sample size, the inability (in most cases) to characterize health risks, difficulties in interpretation—particularly regarding health risks—and so on. Thus, it is essential to rigorously assess the relevance and feasibility of an exposure study in order to ensure that its results are both meaningful for the affected populations and usable by local authorities in their management of the pollution under study. This guide offers methodological guidance on assessing the relevance and feasibility of a local-scale exposure study, as well as on managing its implementation when conditions are met. It details the practical procedures to be followed for an exposure study and its interpretation. In particular, it includes criteria for the inclusion and exclusion of individuals, population recruitment, the questionnaire accompanying the collection of biological samples, the organization of sample collection, their transport and storage, criteria for selecting the analytical laboratory, and principles for interpreting the results, as well as the associated statistical aspects. Local pollution is a source of concern for affected residents. In this context, the implementation of a local-scale exposure study is likely to generate significant expectations from residents and local authorities. It is therefore crucial to involve them in the various stages of the study, from its design to the reporting of results. This guide thus provides key insights for establishing ongoing dialogue and appropriate communication with residents and local authorities, including a list of frequently asked questions specific to soil contamination studies conducted in the context of local pollution. Finally, this guide emphasizes the importance of complying with regulatory requirements and safety measures.