Novel Drug delivery System (NDDS) refers to the approaches, formulations, technologies, and systems for transporting a pharmaceutical compound in the body as needed to safely achieve its desired therapeutic effects. NDDS is a system for delivery of drug other than conventional drug delivery system. The aim of this chapter is to review the literature for SMART nanocarrier-based delivery systems and extended controlled release DDSs which maintain the concentration of the drug within the therapeutic window for a longer time, thereby lowering the frequency of administration. Also, microfluidics (MF), one of the most recent fabrication methods used to design and prepare NDDSs has been discussed. MF can be used to create innovative pharmaceutical formulations and can also be applied to other biological and diagnostic purposes. Transfersomes possess an infrastructure consisting of hydrophobic and hydrophilic moieties together and as a result can accommodate drug molecules with wide range of solubility. The high and self-optimizing deformability of typical composite transfersomes membrane, which are adaptable to ambient tress allow the ultra-deformable transfersomes to change its membrane composition locally and reversibly, when it is pressed against or attracted into narrow pore. Transfersomes can deform and pass-through narrow constriction (from 5 to 10 times less than their own diameter) without measurable loss. This high deformability gives better penetration of intact vesicles. They can act as a carrier for low as well as high molecular weight drugs e.g. analgesic, anesthetic, corticosteroids, sex hormone, anticancer, insulin, gap junction protein, and albumin. Keywords: Transferosomes, Novel Drug Delivery System, Phospholipids, Sonification, Interferon.