This study brings attention to the determinants of 21st-century skills and 21st-century digital skills. The following skills are investigated: technical, information, communication, collaboration, critical thinking, creativity, and problem-solving skills. To understand differences in the level of these skills among workers, we need to know the factors that determine an individual’s skill level. A systematic literature review was conducted to provide a comprehensive overview of empirical studies measuring skill determinants. The results show that there is strong need for research on determinants of communication and collaboration skills. In a digital context, determinants for creativity and critical thinking are hardly studied. Furthermore, the identified determinants of 21st-century skills studies are limited to personality and psychological determinants, neglecting, for example, social determinants such as social support. Although digital skills studies show more variety, they mostly cover demographic and socioeconomic determinants.