Post-disciplinary and transdisciplinary knowledge synthesis facilitates extensive intellectualization, socialization, personalization, and naturalization of next-generation cyber-physical systems (NG-CPSs). However, it makes learning and teaching NG-CPSs more challenging and calls for new educational methods. These challenges arise because (i) conceptual familiarization with these systems must start in basic education for attitudinal reasons, (ii) proficiency in technologies and system development must continue through undergraduate, graduate, and postgraduate levels, and (iii) keeping pace with the evolution of NG-CPSs requires lifelong learning skills and efforts. The goal of the research was to critically review the current state of the art, reveal the related epistemological and computational issues, examine pedagogical and andragogical concepts, and propose specific approaches based on innovative mental and procedural models. A thorough and systematic literature review was conducted, guided by five main research questions. After clarifying the specific objectives, this treatise, rendered as an argumentative position paper, offers a notional clarification to support a consistent interpretation of foundational concepts and definitions, and their relationships. This is necessary due to the prevailing confusing terminology and frequent differences in concept interpretation. The core features and manifestations of the system paradigm of CPSs are analyzed, and a conceptual model illustrating the strands of paradigmatic evolution of CPSs is proposed. Finally, an overview of the likely operations and characteristics of NG-CPSs is provided. The knowledge components mentioned above are vital not only for informing readers about the state of the art in CPSs but also for establishing a solid foundation for pedagogical advancements.