In late 2020, the National Reference Center for Streptococci reported to Santé publique France the identification of several cases of infections—both invasive and non-invasive—caused by an emerging strain of Streptococcus pyogenes of the emm60.11 genotype. The first cases were identified between March and September 2020 in four regions of metropolitan France, including several in the Lille metropolitan area in Hauts-de-France. They primarily involved young adults, people who inject drugs, or those experiencing homelessness. In the Hauts-de-France region, investigations and enhanced epidemiological surveillance were implemented to guide management and prevention measures aimed at halting the transmission chain and preventing the risk of a virulent bacterial strain becoming established within this vulnerable community. These measures were combined with an optimization of diagnostic and medical care pathways to reduce the frequency of severe invasive forms and prevent the emergence of resistance to first-line anti-infectives, given the difficulties with treatment adherence often reported among patients in extreme precariousness. The management of this outbreak, carried out in partnership with key stakeholders in the fields of extreme poverty and substance use, has so far led to a sustained decrease in new cases of infection and, most importantly, a significant reduction in the severity of clinical manifestations of Group A Streptococcus (GAS) infections, across all genotypes, within the community of homeless individuals with substance use disorders.