Objectives: This study aimed to: (a) determine the levels of burnout, secondary traumatic stress, and compassion satisfaction among intensive care unit nurses at the university hospital in Sfax, Tunisia, and (b) explore the relationship between resilience and the three dimensions of professional quality of life in this nursing specialty. Design and methods: This was a descriptive and predictive study using validated self-reporting instruments: Professional Quality of Life Scale version 5 and Brief Resilience Scale. Multiple regression using stepwise solution was employed to explore the relationship between resilience and the three dimensions of professional quality of life (burnout (BO), compassion satisfaction (CS), and secondary traumatic stress (STS)). Statistical significance was set at p < 0.05. Results: The results revealed that 61.3%, 63.2%, and 47.2% of ICU nurses were in the moderate range for BO, CS, and STS, respectively. Resilience score was the critical predictor contributing to Professional Quality of Life subscales scores: Burnout (β = −0.26, p = 0.001), secondary traumatic stress (β = −0.23, p = 0.001) scores were negatively predicted by resilience score. However, CS score was positively predicted by resilience score (β = 0.28, p = 0.002). Conclusion: The current study’s findings support the argument for the development of training programs to promote psychological resilience among ICU nurses in order to improve the quality of professional life.