Objective: This study aims to explore the interrelations between joy at work, vocational identity, and COVID-19-related latent variables. Design: A cross-sectional design was adopted to survey 253 registered nurses through nursing organizations and social networking sites during the time of the COVID-19 pandemic. Methods: Structural Equation Modeling through Partial Least Squares (SEM-PLS) was employed to accurately analyze and estimate relationships among joy at work, vocational identity, and COVID-19-related constructs in compliance with published standards and guidelines. Results: Thirty-one items received convergent validity measures to represent the five study constructs related to joy at work, vocational identity, and Work life Impact of COVID-19 pandemic: Meaning, Engagement, and Growth (MEG), Compassion, Sensitivity, and Respect (CSR), Trust, Support, and Flexibility (TSF), Vocational Identity Questionnaire (VIQ), and Work life Impact of COVID-19 pandemic (CI). The generated model exhibited good model fit and consistent quality indices. The data fit statistically with the model: (Average Path Coefficient = 0.195, p < 0.000); Average R-Squared = 0.156, p < 0.003; Average Adjusted R-Squared = 0.151, p < 0.004; Average Variance Inflation Factor = 2.193 (within the ideal range); Average Full collinearity VIF = 2.388 (within the ideal range), and Tenenhaus Goodness of Fit (GoF) = 0.329. The perceived Work life Impact of COVID-19 pandemic (CI) was a significant predictor of joy at work constructs (MEG, CSR, and TSF) and VIQ with direct effects. It also exerted a negative influence over MEG and TSF, but positively on CSR and VIQ. Notably, joy at work constructs significantly mediated the effects of CI on VIQ. Conclusion: A structural model was developed that offers insights and a parsimonious explanation for the interrelations of COVID-19, joy at work, and vocational identity variables. The pandemic unquestionably influences the nurses' perceived joy, sense of calling, and meaning in life's work, and joy at work enhances nurses' work-life worth during challenging times. Clinical Relevance: An increased understanding of nurses' joy at work during challenging times can potentially influence work culture, informs individual nurses, nurse leaders, and healthcare systems in all professional domains of practice and provides the foundational information to identify barriers to joy and strategies that enhance joy.