The current state of the healthcare sector in developing countries such as Nigeria has resulted in a significant number of highly skilled health workers migrating overseas for a more fulfilling career. Stakeholders are concerned about this development, emphasizing its impact on healthcare service delivery. While some studies point to role conflict and a lack of family support as the primary causes of female nurses' unsustainable careers, others claim that individual, contextual, and institutional factors can all impact career sustainability. Various factors influence an individual's career sustainability, such as their career skills, ability to work in a team, and confidence in performing tasks successfully. This study aimed to investigate the relationships between these variables and their impact on the sustainability of careers among female nurses. The study is grounded on the Social Cognition Career Theory as its theoretical foundation. This quantitative study analyzed a sample of 292 female nurses from a tertiary hospital in southwest Nigeria using IBM SPSS 28 and Smart PLS. The data was obtained from a questionnaire and analyzed through measurement and structural models. The study found that the professional development of career competence had a significant and positive causal relationship with the career sustainability of female nurses. However, teamwork had a negative effect on the career sustainability of the female nurses surveyed. Furthermore, the mediation analysis revealed that self-efficacy played a positive mediating role in the relationship between teamwork, competence development, and career sustainability. Study findings provide insight into how stakeholders in Nigeria's healthcare system might improve career sustainability by boosting professional career competence, increasing team effectiveness, and encouraging career self-confidence among nurses. To maintain a stable career, this study recommends that nurses focus on enhancing skills, working effectively in a team, and building self-confidence.