Background: The Job Demands and Resources (JD-R) model is used to examine predictors of well-being, work engagement, and individual or organizational outcomes. According to the model, work engagement and communication skills play a mediating role between work-family conflict and resilience to job satisfaction in nurses. Methods: A cross-sectional study was conducted considering 431 Peruvian nurses of mean age ( M = 40.31 years; SD = 10.94) ranging from 22 to 68 years working in public hospitals in the Lima region. Data were collected using a self-reported form of the Job Satisfaction Scale, communication skills, work engagement, work-family conflict, and resilience. The theoretical model was evaluated using structural equation modeling (SEM). Results: A theoretical model with adequate fit was obtained [χ2(2) = 6.0, P < .001, CFI = 0.995, RMSEA = 0.068, SRMR = 0.015]. Results indicated an inverse relationship between work-family conflict with communication skills (β = −.24, P < .001) and work engagement (β = −.10, P = .003). Likewise, resilience had an influence on communication skills (β = .55, P < .001) and work engagement (β = .33, P < .001). In addition, the model explains 71% of job satisfaction. Also, the results indicate the influence of work-family conflict and resilience through the mediating role of work engagement and work-family conflict on job satisfaction. Conclusions: The model confirmed that work engagement and communication skills are valid moderators to mitigate work-family conflict and strengthen resilience that favors job satisfaction in nurses.