The article analyzes the implementation of active learning methodologies, with a particular focus on Problem-Based Learning (PBL), within the teaching of natural sciences. Based on the theory of Meaningful Learning, Significant Learning Experiences (SLE) are discussed as a means to promote a deep and contextualized understanding of scientific concepts. Furthermore, the integration of the STEM approach, which combines science, technology, engineering, and mathematics, into PBL is examined, highlighting how this approach facilitates the development of critical skills, such as computational thinking, and encourages the practical application of scientific knowledge. The use of emerging technologies and Digital Educational Resources (DER) is presented as a key tool to enrich the learning process, allowing students to conduct simulations, virtual experiments, and collaborate on research projects. The article also addresses the challenges and opportunities that these methodologies present, particularly concerning technological infrastructure and teacher training. Finally, the importance of transformative teaching practices and the creation of collaborative networks among educational institutions to maximize the impact of the STEM approach in education is emphasized. Projections indicate a promising future for these methodologies, with significant potential to prepare students not only for technical careers but also to be informed citizens capable of contributing to social and scientific progress.