Nanofillers (NFs) are used in various pharmaceutical formulations to achieve desired drug delivery system (DDS) properties for successful drug delivery goals; to win over their intrinsic limitation of DDS. By nature, NFs have diverse characteristics, are conveniently prepared, and are cost-effective. Nanofillers includes organic, inorganic, carbon, nanocomposite materials and materials from other categories. Most of the nanofiller are lighter, durable, versatile, and are reliable for various applications. New types of materials such as metal oxide framework, 3D bioprinted, MXenes, and hydroxy apatite, are emerging, with excellent drug delivery applications. Nanofiller applications in various DDS such as hydrogels, tablets, wound dressings, films and membranes, microneedles, soft nongelation capsules, and microparticles are reviewed. Major applications are reported for hydrogels and transdermal delivery systems. Incorporation of NFs enable smart drug delivery to modulate release such as pulsatile release, improved release, and sustaining the release achieved. Smart drug deliveries such as dual responsive, triggerable, on demand, shape memory, enhanced drug encapsulation are enabled by NFs. Nanofillers preprepared using different methods, which have an effect on its properties, which in turn have an effect on DDS performance. Therefore, control of its physicochemical properties is essential. Various techniques used for characterization of the NFs such as spectroscopic, thermal, and advanced microscopy. Various aspects of NF use in hydrogel and films/membrane DDS are mentioned in brief. Future scope for NFs in DDSs and possible limitations are discussed. Regulatory approvals are essential and the relevant global scenario is discussed in brief.