This paper draws on research analyzing the emotional and relational impacts of poverty and exclusion on charities’ clients in Spain since the 2008–2009 economic crisis, including people experiencing multiple exclusion homelessness (MEH). The study adopts a mixed-methods approach in which twenty in-depth cases were collected in different geographical locations, including twelve cases experiencing MEH. Unlike other disadvantaged groups, those affected by MEH suffer material shortages, traumatic experiences, psychological disorders, physical illnesses, and a high degree of relational vulnerability, as reflected in the structure and composition of their personal networks, which tend to be smaller in size, with just a few weak and temporary contacts, and with care professionals playing an important role. These charity users often need long-term socio-sanitary care, which challenges public and private health-care systems. Therefore, our contribution to this Special Issue is directed toward improving understanding of the relational characteristics of severely excluded people, how social support affects their personal networks, and the challenges this assistance poses to care services.