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Responsive educational proposals to develop skills to meet the demands of Industry 4.0 have become imperative to guarantee inclusive, equitable, and quality education and promote lifelong learning opportunities for all, also reducing the negative impact of COVID-19 and the major post-pandemic social issues. This article analyzes which components of Education 4.0 have been considered in 21st century skills frameworks and identifies the teaching and learning methods and key stakeholders impacted. We conducted a systematic literature review (SLR) with research questions to highlight studies that address 21st century frameworks worldwide, identifying which teaching-–earning strategies contain 4.0 components, their learning dimensions, and the targeted stakeholders. The findings allowed us to identify opportunities to create or improve 21st century skills frameworks with the required Education 4.0 components to develop future skills. Our study revealed the absence of these frameworks for teachers and schools. Most are oriented toward students, developing competencies through the dimensions of character, meta-learning, and linking active learning teaching strategies. This work presents studies incorporating innovative educational practices and the core Education 4.0 components. It concludes with a reflection on creating educational models to develop complex-reasoning competencies and auto-systemic thinking to support problem-solving and address social needs.