For many diseases, a promising prognosis is often linked to the ability to deliver therapeutic agents to specific sites in the body. In chemotherapy, this is often challenging because cancer drugs are distributed throughout the body, provoking damage to healthy cells and, therefore, side effects. Moreover, some cancer drugs are hydrophobic and require formulation to be used in the clinic, while macromolecules such as RNApotentially, the most effective cancer therapeutics that existrequire a vehicle to avoid in vivo degradation. Without a doubt, drug deliveryi.e., bringing an agent from outside a biological system to a specific site within the body has rightfully been identified as a critical area of research and is indeed the bottleneck for the translation of genetic therapies to the clinic. In this context, the engineering of nanomaterials has emerged as an interesting avenue for improved disease diagnosis and treatment. The encapsulation of therapeutic agents in nanoparticles has improved their stability and solubility, augmented their ability to penetrate membranes, and increased their circulation times, enhancing treatment efficacies. Despite these superior capabilities, massive investment, and decades of research, the number of clinically approved nanomedicines is below projections, partly attributed to a gap in outcomes between pre-clinical data (in vitro and in vivo) and human studies. These poor therapeutic outcomes are associated with complex biological barriers that serve to limit the bioavailability of therapeutic agents at diseased sites. While initial iterations of nanomaterials engineered for drug delivery have failed to overcome these barriers, an improved understanding of the interactions of nanoparticles with biological systems , and clever advances in engineering have seen several nanoparticle formulations being approved for clinical usage. State-of-the-art drug delivery formulations can broadly be classified as lipidbased, polymer-based, and inorganic nanoparticle-based. Despite their advantages however, these formulations either have poor targeting capabilities or face solubility, toxicity, and aggregation concerns. In view of these constraints, and owing to their inorganic-organic crystalline nature, metal-organic frameworks (MOFs) emerged as a new system for drug delivery. Composed of inorganic nodes connected via organic linker molecules, MOFs have well-defined, tunable structures with high void space and permanent porosities. While these unique characteristics allow MOFs to be utilized in a variety of applications such as gas storage and separation, sensing, and catalysis, with regards to drug delivery, these materials have significant advantages over currently utilized formulations. The biggest advantage is that the high void space allows the encapsulation of up to 50 times higher quantities of therapeutic agents per unit mass (up to 1.4 g drug per g MOF), which are released over long timescales. The open structure of MOFs many times implies relatively low stability compared to conventional porous materials such as zeolites and activated carbons but, in drug delivery, it is beneficial as it will avoid bioaccumulation. Secondly, the unique chemistries of the organic and inorganic components can be leveraged to incorporate multiple functionalities onto the MOFs' internal or external surface. An avenue of particular interest is the functionalization of the external MOF surface post-synthesissometimes referred to as biofunctionalization which improves colloidal stability, extends release times, and enhances cellular uptake, in an attempt to achieve targeted drug delivery. Moreover, these surface-modified MOFs showed improved intracellular stability, lower cytotoxicity in vitro, and delayed release times. Despite advancements over the past decades, there are some gaps that are yet to be filled before MOFs can be considered at a clinical level.