Compared to traditional medication dosage forms, nanocarrier-based delivery systems confer several benefits, including drug protection, improved bioavailability, and tailored administration to disease sites. With increased availability in the body, better drug loading values, improved intracellular transport, and superior physiological outcomes, nanocarriers are reported to improve targeted drug delivery to cells and tissues. Stimuli-responsive nanocarriers with unique design characteristics can adapt to exogenous and endogenous stimuli; their structure and physicochemical properties change in response to various factors. This results in the release of drugs at a specific target site when triggered by certain physiological or external triggers. Numerous therapeutic and diagnostic processes can be made substantially more effective by creating pharmaceutical nanocarriers with multiresponsive systems. The most popular technique for giving drug nanocarriers stealthy characteristics is PEGylation. The PEG molecules have been altered to improve their uptake by particular targets and to allow controlled drug release. This chapter highlights the most recent developments in nanocarriers with multifunctional properties and stimuli sensitivity for therapeutic drug delivery applications. By delivering the drugs specifically to the disease cells, there is a pronounced enhancement in the efficacy of the treatment, improving the incidence of unwanted effects on nontarget cells, tissues, and organs.