21st-century skills are key words which have been most searched in recent past. Yet, there seems to be amiss on how teachers should be prepared to teach 21st-century skills. Limited research insights imply lack of actionable inputs for design of teacher education programmes. Thus, this study supports the call by reviewing 55 relevant studies, using the systematic literature review (SLR) approach. This study employed a stringent search protocol to confine search to two popular databases—Scopus and Web of Science (WOS). The authors identified two emerging themes and six sub-themes. The three sub-themes under the first theme upskilling and reskilling of in-service teachers in 21st-century skills are: (1). training initiatives, (2). teachers’ experiences in teaching 21st-century skills, and (3). teachers’ perceptions and skill assessment. The other three sub-themes under the second theme professional development of pre-service teachers and 21st-century skills are: (1). pedagogical approaches, (2). technology-based teaching-learning of 21st-century skills, and (3). experience, competence and proficiency in 21st-century skills. Findings suggest the need to focus on targeted interventions, pedagogical tools and resources and peer-based learning, and recommend expanding the list of keywords searched under this study by including specific 21st century skills such as creativity to add a new dimension to their review.