Previous research has shown that social climate (SC) is important for the daily life of youths living in therapeutic residential youth care (TRC). However, little is known on how SC can promote a positive quality of life (QoL) for the heterogeneous TRC population. This study, therefore, investigates how TRC and youth characteristics are associated with SC and QoL. We employed a combination of person-centered and variable-centered approaches in a cross-sectional design using a sample of 400 Norwegian youths. We used previously established TRC and youth classes in a structural equation model, where these classes were regressed on latent SC and QoL. Both direct and indirect effects were analyzed. All youth classes were associated with SC and QoL, such that youth with family problems, incidental problems, and the migrant background class scored higher on SC and QoL compared to the severe problems class. In addition, SC mediated the association of the incidental problems and migrant background classes on QoL. TRC staff should acknowledge that a positive SC