Homeless persons and migrants in precarious housing conditions are vulnerable populations that have been peculiarly impacted by the Coronavirus Disease 19 (COVID-19) pandemic. These populations are more at risk of contracting COVID-19 as they often find it difficult to adhere to public health directives and, if exposed, may be more susceptible to illness or death due to the higher prevalence of underlying physical and mental comorbidities compared to the general population. In addition, vulnerable populations may have limited access to essential diagnostics and treatments, thus leading to untreated COVID-19 cases and their development into more severe forms. Health, social and government agencies should collaborate to develop services that support these communities, in accordance with the World Health Organization principles. Migrant and homeless centers have a central role, as they provide a significant contribution to prevent infection spread and favor access to early medical treatment to those affected, thus preventing more severe forms of infection.