Introduction Increased stressors and decreased job satisfaction are major challenges in nursing. Important factors of better professional quality of life include compassion satisfaction, burnout, and secondary traumatic stress. It is critical to assess these factors to help improve nurses’ clinical practices. Objective The purpose of this study was to determine the relationships between the three factors and associated factors. Methods A cross-sectional, multisite study was conducted on a convenience sample of 464 nurses working at three public hospitals in Saudi Arabia. The Professional Quality of Life Version 5 was used to collect data. Bivariate and multivariate analyses were run using SPSS. Results Scores were slightly moderate on the compassion satisfaction, burnout, and secondary traumatic stress levels. Compassion satisfaction was statistically significantly and negatively associated with burnout. A statistically significant relationship was reported between compassion satisfaction and secondary traumatic stress. Further, there was a statistically significant association between burnout and secondary traumatic stress. In regression, only the secondary traumatic stress model was statistically significant. Conclusions Nurse managers should use highly standard guidelines to reduce secondary traumatic stress levels. Further actions addressing potential issues for improving compassion satisfaction and reducing burnout levels among nurses are also recommended.