Recently, drug delivery strategies based on nanomaterials have attracted a lot of interest in different kinds of therapies because of their superior properties. Polydopamine (PDA), one of the most interesting materials in nanomedicine because of its versatility and biocompatibility, has been widely investigated in the drug delivery field. It can be easily functionalized to favor processes like cellular uptake and blood circulation, and it can also induce drug release through two kinds of stimuli: NIR light irradiation and pH. In this review, we describe PDA nanomaterials' performance on drug delivery, based on their size, morphology, and surface charge. Indeed, these characteristics strongly influence the main mechanisms involved in a drug delivery system: blood circulation, cellular uptake, drug loading, and drug release. The understanding of the connections between PDA nanosystems' properties and these phenomena is pivotal to obtain a controlled design of new nanocarriers based on the specific drug delivery applications.