Background Working in the perioperative context is complex and challenging. The continual evaluation in this environment underscores the need for adaptability to technological advancements, and requires substantial allocation of resources for training and education. This study aimed to explore personality characteristics of nurse anesthetists and surgical nurses that are instrumental for sustainable employability in technologically advanced environment. Methods Exploratory, cross-sectional survey study including nurse anesthetists and surgical nurses, both certified and in training, and a sample of the normative Dutch population. Personality characteristics were identified with the Big Five Inventory, which consisted of 60 items answered on a five-point Likert scale (strongly disagree to strongly agree). Results Specific personality traits were found for nurse anesthetists and surgical nurses when compared to the normative Dutch population. Traits of both nurse anesthetists and surgical nurses differed significantly on all domains of the Big Five Inventory, with the largest differences found within the dimension negative emotionally. Conclusions This study highlights the role of specific personality traits in maintaining employability within the rapidly evolving and technologically advanced landscape of healthcare. It emphasizes the relationship between individual traits and professional excellence, being crucial educational strategies for overall improvement in healthcare.