Work engagement, professional quality of life (ProQOL), and intent to leave (ITL) significantly impact organizational behaviors and outcomes. Understanding the complex interrelationships among nurse work engagement, ProQOL, and ITL is essential for improving nurse retention, job satisfaction, and patient outcomes. In previous investigations, work engagement, ProQOL, and ITL relationships have primarily been analyzed individually. A more integrated approach is needed to gain a comprehensive understanding of these factors in the nursing profession. This study was designed to evaluate the interrelationships among work engagement, ProQOL (compassion satisfaction [CS], burnout, and secondary traumatic stress [STS]), and ITL in nurses using structural equation modeling path analysis. This was a quantitative descriptive study. Data were collected from registered nurses in the United States (n = 900) using the Utrecht Work Engagement Scale, the ProQOL-5 (CS, burnout, and STS), and a demographics datasheet (including a one-item ITL question). The proposed theoretical model, incorporating major constructs, was tested using structural equation modeling. Level of work engagement in nurses impacts ITL through ProQOL. Among the mediating variables, burnout (0.31) had the largest total effect on ITL, followed by STS (0.12) and CS (-0.12). Burnout and STS were found to correlate with ITL directly, whereas CS was found to correlate with ITL indirectly. Promoting work engagement, addressing burnout and STS, and fostering CS can positively influence nurse retention and job satisfaction, ultimately improving patient care quality. Healthcare leaders and policymakers should implement strategies to enhance nurse engagement, reduce burnout, and cultivate compassion satisfaction to increase nurse retention and improve organizational outcomes.