Skills needed to be successful in the world have changed, and there is a gap between those learned at school and those required to function at work and in society. A broader range of skills is required to learn, communicate, collaborate, and solve problems in digital environments. Twenty-first century skills have been identified by UNESCO, OECD, and others as competences required for a sustainable future of the knowledge society. The aim was to learn the design principles involved in the incorporation of these skills into the curriculum, find out possible ways to teach and assess them, and examine how this process could be personalized using Information and Communications Technology (ICT). A literature review was carried out through a qualitative metasynthesis, which identified 43 studies that met the inclusion criteria. From the in-depth analysis, it can be seen that although the incorporation of 21st century skills into the curriculum, teaching methodologies, and the use of ICT are all recurrent themes, there is still a need for further research into the design and implementation of new instruments for assessment and the ways in which the teaching–learning process can be personalized.