Medical social workers (MSWs) operate in emotionally demanding and high-pressure environments, rendering compassion satisfaction critical for their well-being and career sustainability. This study examines the links between perceived social support and compassion satisfaction, focusing on the mediating roles of general physical health and resilience. A cross-sectional survey was conducted among 319 medical social workers in the Chinese mainland. Data were analyzed using Pearson correlation and sequential mediation modeling. Results indicated that perceived social support was positively associated with compassion satisfaction. While resilience independently partially mediated this relationship, a significant sequential mediation pathway was also identified: perceived social support was related to physical health, which in turn was linked to resilience and, ultimately, compassion satisfaction. These findings extend existing research by unveiling an interconnected ‘Relationship-Body-Mind’ pathway, emphasizing that physical health and resilience act as crucial resources. Interventions aiming to sustain medical social workers’ well-being should adopt integrated approaches that simultaneously target social, physical, and psychological resources.