In the evolving landscape of nanotechnology, hybrid silica nanoparticles (HSiNPs), metal ion hybrid silica nanoparticles (MI-HSiNPs) and its functionalized and composites have emerged as a groundbreaking innovation, especially in the realm of medical applications. The integration of metal ions with silica NPs not only augments their physicochemical properties but also enhances their functionality in various biomedical applications. This review delves into the recent advancements in the synthesis and application of HSiNPs, emphasizing their pivotal role in revolutionizing therapeutic approaches, particularly in targeted drug delivery and diagnostic imaging. Metal ions, when incorporated into silica NPs, impart unique optical, magnetic, and catalytic properties that can be harnessed for therapeutic purposes. The synthesis of MI-HSiNPs typically involves methods like co-condensation and post-synthesis grafting, which allow precise control over the NPs' size, shape, and metal ion distribution-critical factors that influence their biological interactions and therapeutic efficacy. This precision facilitates the development of NPs that can effectively target diseased cells with minimal off-target effects, a significant advancement over traditional treatment methods. © 2025 The Authors