Architectural design of biomaterial structures is essential to reach the full/potential of the materials' chemical and biological properties. Clinically, these properties depend on the targeted applications of delivery, such as tissue regeneration, imaging, or cancer. To get an efficient material for biological applications, key properties are needed, such as degradability, low toxicity, cell specificity, relative efficiency, and capability of delivering multiple molecules. In recent years, significant progress has been made through either the design of the material itself (synthetic or natural polymers, dendrimers, crosslinking) or the fabrication technique (nozzle reactor, emulsion, and template). The combination of these materials and techniques results in a large variety of biomaterials that have varied shape and physico-chemical and biological properties. Nevertheless, these inherent properties are not sufficient and interest in discovering and developing new techniques that present these biomaterials in different light is now under focus. A useful strategy to prepare biomaterials with unique and novel architectures is through the use of templates that have defined geometrical features. This holds great promise, especially for the development of hollow structures, such as spheres. The nanoscale structural design of biomaterials via the use of templates and their potential clinical applications are discussed. In addition, the conceptual hurdles that must be overcome to produce applications that are clinically relevant are examined.