<p>Bone regeneration remains a critical challenge, especially in complex defects where conventional pharmacological and surgical treatments are inadequate. This review critically evaluates recent progress in micro- and nanoscale biomimetic scaffold systems and stem cell technologies, highlighting how structural design at the micro/nano level directly influences stem cell fate and osteogenesis. We analyze advances in fabrication techniques including 3D bioprinting, electrospinning, and micro/nanofabrication that enable hierarchical porosity, controlled surface nano-topographies, and dynamic biochemical environments. Particular attention is given to structure–function relationships, where scaffold mechanics, biochemical cues, and spatial patterning govern mesenchymal stem cell (MSC) adhesion, proliferation, and differentiation. Unlike conventional descriptive accounts, this review emphasizes both the therapeutic potential and the unresolved limitations of current approaches, such as reproducibility, host integration, and immunomodulation. Finally, we outline future perspectives in AI-driven scaffold design, and smart biomaterials, providing a roadmap for the translation of biomimetic scaffold–stem cell systems into clinically effective bone regeneration strategies.</p>