This document provides a framework to facilitate the interpretation and use of data from SARS-CoV-2 genomic surveillance in wastewater in France for public health and management purposes. Wastewater surveillance should be viewed as a complement to population-based surveillance using individual health data, but should not replace it. It represents Santé publique France’s contribution in response to a request from the Directorate General for Health regarding the epidemiological aspect to define the need for a useful indicator for surveillance. On this basis, it must be supplemented by a microbiological component (sampling, analysis). It is based on experiments conducted in France and other countries, as well as recommendations from the WHO, the U.S. CDC (Centers for Disease Control and Prevention), the Netherlands, and the European Commission (EU 2021/472 of March 17, 2021). As wastewater monitoring is a rapidly evolving field, the guidelines proposed in this document may need to be updated as knowledge advances.