Nanostructured drug delivery formulations have lately gained enormous attention, contributing to their systematic development. Issuance of quality by design (QbD) guidelines by ICH, FDA, and other federal agencies, in this regard, has notably influenced the overall development of drug products, enabling holistic product and process understanding. Owing to the applicability of QbD paradigms, a science lately christened as formulation by design (FbD) has been dedicated exclusively to QbD-enabled drug product development. Consisting of the principal elements of design of experiments (DoE), quality risk management (QRM), and QbD-enabled product comprehension as the fundamental tools in the implementation of FbD, a variety of drug nanocargos have been successfully developed with FbD paradigms and reported in the literature. FbD aims to produce novel and advanced systems utilizing nominal resources of development time, work effort, and money. A systematic FbD approach envisions the entire developmental path through pivotal milestones of risk assessment, factor screening and optimization (both using appropriate experimental designs), multivariate statistical and optimum search tools, along with response surface modeling, usually employing suitable computer software. The design space is one of the fundamental elements of FbD providing the most sought-after regulatory flexibility to pharma companies, postapproval. The present paper provides a bird's eye view of the fundamental aspects of FbD terminology, methodology, and applications in the development of a wide range of nanocargos, as well as a discussion of trends from both technological and regulatory perspectives.