This study investigates the link between the Big Five personality traits and the well-being of teleworkers while considering potential gender differences. The sample consisted of 230 teleworkers who answered an online questionnaire. Then, a path analysis was employed to explore the relationships between the variables. Findings indicate that distinct personality traits can affect employees’ attitudes towards teleworking, with a discernible impact on their subjective well-being. While both genders exhibit similar patterns of relationships between personality traits and telework outcomes (positive feelings for extraversion and agreeableness, and negative feelings for neuroticism), there are differences in the magnitude and significance of some of these relationships, particularly in the case of conscientiousness, where its impact on negative feelings towards telework is more pronounced for men. Findings have important practical implications for organizations and individuals in the evolving work landscape.