Repetitive outbreaks and prolonged epidemics represent mortal threats to global health, creating chaos in our globalized world. To date, scientists have been compelled to follow FDA guidelines for conventional clinical trials, which decelerates the release of effective therapies to battle outbreaks and safeguard global health security. Developing multi-purpose platform nanotechnologies to self-target specific organs in response to the disease microenvironment could greatly help to rapidly anticipate and efficiently manage outbreaks. Nano-interventions in the form of self-targeting nanoparticles (NPs) could accelerate the clinical translation of potential drugs to fight future outbreaks via innovating their clinical trials. This review sets the foundation of the self-targeting concept to govern the in vivo fate of NPs without the need to complicate the engineering designs with targeting ligands. The proposed catalogue of accelerated nano-innovations offers self-targeting, physiological trafficking, bio-compliance, and controllable drug release in response to associated smart linkers.