Generation Z is known to have a high concern for work-life balance and mental health. In a hospital work environment that demands physical and emotional resilience, work imbalance and high levels of burnout have the potential to reduce loyalty, especially for nurses who deal directly with patients. This study aims to examine in depth the effect of work-life balance and burnout on the loyalty of Gen Z nurses at Dera As-Syifa Hospital, Banjarharjo. The research method used is quantitative with an explanatory research design, involving 111 Gen Z nurses as respondents through a total sampling method. Data were collected using a Likert-based questionnaire, then analyzed by multiple linear regression using SPSS. Before the analysis, validity, reliability, and classical assumption tests were conducted to ensure the feasibility of the instruments and models. The results showed that partially, the work-life balance variable (X1) has a positive and significant effect on loyalty (Y), with a calculated t value of 12.814 greater than the t table of 1.982 and a significance value of 0.000 <0.05. Meanwhile, the burnout variable (X2) had a significant negative effect on loyalty, with a calculated t-value of -2.109, greater than the t-table of 1.982 (in absolute value) and a significance value of 0.037 <0.05. Simultaneously, these two variables contributed 60.7% to the variation in loyalty among Gen Z nurses, while the remaining 39.3% was influenced by factors outside the research model. This finding underscores the importance of hospital human resource management in addressing work-life balance and managing burnout levels to maintain nurse loyalty. Strategies to improve work well-being, psychological support, and workload adjustments are key to creating a healthy and sustainable work environment for Generation Z nurses.