The comprehensive analysis of the impact of job demands and job resources on burnout among Certified Registered Nurse Anesthetists (CRNAs) in the U.S. utilized a sample of 152 CRNA participants who responded to an online electronic survey administered by the AANA. The JDR theoretical framework guided hypotheses development. Structural Equation Modeling (SEM) methods validate the proposed hypotheses. The findings are instrumental in understanding the interplay between job demands and job resources in relation to burnout within the CRNA cohort.Descriptive statistics highlighted the distribution of job-related stress and support measures, with the Oldenburg Burnout Inventory scores indicating a moderate level of burnout among participants. Correlation analysis revealed significant relationships between job factors and burnout dimensions, with collaboration, decision latitude, and organizational support negatively correlated with exhaustion and disengagement, suggesting their potential protective effects against burnout. The SEM analysis provided a robust framework for assessing the direct and indirect correlations between job demands, job resources, and burnout. The regression paths confirmed job demands as a strong predictor of burnout, with a significant positive effect. Job resources exhibited a complex relationship with burnout, with an indirect buffering effect that did not reach statistical significance in the mediation analysis, although the overall relationship between job demands and burnout was significant. The results underscore the significance of job demands as predictors of burnout among CRNAs and illuminate the nuanced role of job resources. This lays a fertile ground for future research to build upon, potentially leading to targeted interventions aimed at mitigating burnout among CRNAs and policy revision and changes that ensure CRNAs have access to needed resources and supports related to job demands.