The aim of the study is to explore the relationship between Greek teachers' perceptions regarding their professional quality of life and their sense of efficacy. Further, the moderating effect of life satisfaction between the dimensions of compassion fatigue (burnout and secondary traumatic stress) and teachers' sense of efficacy is investigated. The sample consisted of 389 primary and secondary teachers living in Athens, Greece. The Professional Quality of Life Scale (ProQOL-5) (Stamm, 2010), the Teachers' Sense of Efficacy Scale (Tschannen-Moran & Hoy, 2001), and the Satisfaction with Life Scale (Townshend, 2023) were used for online data collection. The findings indicated the existence of statistically significant relations between the dimensions of professional quality of life, teachers' sense of efficacy, and life satisfaction. Life satisfaction moderated the interaction between burnout and teachers' sense of efficacy. Results provide a better understanding of teachers' perceptions, contributing to the development and provision of tailored interventions and support.