Polymethylmethacrylate (PMMA) is still the most widely used prosthetic polymer, although its biological inertness and vulnerability to mechanical stress and microbiological colonization are gradually restricting its therapeutic lifespan. This narrative review develops a conceptual framework, three ceramic modifiers corresponding to three distinct biofunctional strategies, to logically guide the design of the next generation of PMMA-based prosthetic dentures. We critically analyze the transformation of hydroxyapatite (HA), silica (SiO₂), and titanium dioxide (TiO₂) from passive fillers to active functional phases, offering unique, complementary therapeutic advantages. Therefore, HA confers osteoconductive and bone affinity, SiO₂ provides surface reactivity, tunable bioactivity, and drug release capacity, while TiO₂ provides mechanical reinforcement, chemical stability, and photocatalytic antibacterial activity. These ceramics used in PMMA matrices result in hybrid materials that outperform standard resins in terms of structural, mechanical, and biological performance. Recent research on binary and ternary systems (e.g., HA–TiO₂, SiO₂–HA, and HA–SiO₂–TiO₂ in PMMA) has indicated synergistic effects, such as increased osteoblast proliferation, reduced biofilm development, improved fracture toughness, and favorable corrosion resistance in simulated oral environments. A decision matrix is also provided to assist the clinician in selecting the best ceramic for a given clinical function of a prosthetic base or provisional repair. Although polymer–ceramic hybrid systems show remarkable translational potential, there are still obstacles to be addressed in terms of long-term interfacial stability, standardized synthesis processes, and regulatory mechanisms. This review proposes a framework of PMMA as a multimodal biofunctional engineering platform rather than a basic structural polymer and provides a roadmap for the development of intelligent, interactive, and clinically durable prosthetic materials.