Mesoporous silica nanoparticles (MSNs) have emerged as versatile nanomaterials with considerable potential in pharmaceutical and biomedical applications because of their highly tunable pore architecture, large specific surface area, accessible surface chemistry, and adaptable particle morphology. Since the development of ordered mesoporous silica materials, particularly MCM-41, considerable progress has been made in controlling particle size, pore diameter, morphology, surface functionality, drug loading, and release behaviour. This review provides a comprehensive overview of the synthesis and recent advances in MSN-based nanomedicine. It discusses the historical development and structural characteristics of MSNs, classification of different MSN architectures, mesopore formation mechanisms, conventional sol–gel and surfactant-templated synthesis, and advanced, emerging, and green synthesis strategies. Particular attention is given to the control of particle size, morphology, pore structure, and surface chemistry because these characteristics strongly influence drug loading, cellular interactions, biodistribution, degradation, and therapeutic performance. The review also examines drug encapsulation and release mechanisms, targeted and stimuli-responsive delivery, and applications in cancer therapy, gene and nucleic-acid delivery, antimicrobial therapy, imaging, biosensing, and theranostics. Recent developments involving multifunctional, biodegradable, responsive, and combination-delivery systems are highlighted. Despite substantial progress, challenges related to reproducible manufacturing, scale-up, long-term toxicity, biodistribution, biodegradation, pharmacokinetics, and regulatory characterization remain important barriers to clinical translation. Future development will require integration of materials science, pharmaceutical technology, toxicology, manufacturing science, and data-driven approaches to establish predictable structure–property–biological performance relationships. Overall, MSNs represent a flexible platform for advanced drug delivery, but their successful translation requires simultaneous optimization of functionality, safety, reproducibility, and manufacturability.