Background <p>Nurses, as core members of the healthcare team, play a crucial role in patient care. Their work engagement directly affects care quality and patient satisfaction. High work engagement not only elevates service quality and safeguards patient safety but also enhances nurses’ job satisfaction and overall well-being. However, empirical evidence on how professional calling influences nurses’ work engagement remains limited. This study examines the mediating role of work motivation in the relationship between professional calling and work engagement among clinical nurses.</p> Methods <p>In this cross-sectional study, stratified random sampling was used to survey 2,924 clinical nurses in Sichuan Province, China, from February to March 2024. Data were collected with demographic questionnaires, the Professional Calling Scale, the Work Motivation Scale, and the Work Engagement Scale. Analyses were performed with SPSS 26.0, comprising descriptive statistics, univariate analysis, correlation analysis, and hierarchical regression. Mediation was tested with Model 4 of PROCESS 4.1.</p> Results <p>The mean work engagement score was 33.63 ± 7.14. Correlation analysis showed that professional calling was positively correlated with work engagement (<i>r</i> = 0.863, <i>P</i> &lt; 0.01) and work motivation (<i>r</i> = 0.877, <i>P</i> &lt; 0.01), and work motivation was positively correlated with work engagement (<i>r</i> = 0.814, <i>P</i> &lt; 0.01). Mediation analysis revealed that work motivation partially mediated the relationship between professional calling and work engagement, with an effect size of 0.199, accounting for 24.8% of the total effect.</p> Conclusion <p>The findings confirm that work motivation mediates the association between professional calling and work engagement among clinical nurses. Nursing managers should therefore foster nurses’ professional calling and strengthen their work motivation to enhance work engagement.</p> Clinical trial number <p>Not applicable.</p>