Mesoporous silica nanoparticles (MSNs) attracted biomedical researchers due to their unique properties like large surface area, pore-volume, and surface-active groups. These properties of MSNs have been broadly explored in drug delivery, photodynamic therapy, biosensors, and tissue engineering in the last decade. The porous nature facilitates higher drug loading into the structural cavities to increase solubility and improve the therapeutic activity thereof. However, the clinical translation of these nanoparticle-based drug delivery systems needs deliberate in vivo human studies to analyze the potential adverse reactions and the side effects on the end user. The studies reported so far have discovered the dependence of toxicity on the characteristic properties such as the shape, size, surface chemistry, and charge of MSNs. In this regard, the MSNs surface properties must be altered or tuned to improve these versatile novel drug delivery systems' biocompatibility. This review summarizes the recent biomedical applications of the mesoporous silica nanoparticle as a potential drug delivery carrier system in the last decade. Advances in the triggered drug release using the concept of gatekeepers and the delivery of large molecules such as protein and nucleic acid are also discussed. Altogether, this article brings together the current research on the MSNs-based drug delivery systems with an emphasis on tunability, surface functional-ization, biosafety, and its clinical translation. This will help a research scientist not only to get a better under-standing of mesoporous silica nanoparticles but also to overcome the associated challenges that need to be addressed during its development from bench to bedside.