The main (and generalistic) advantages and disadvantages of each type of nanosystem have been widely pointed out in literature. However, the advantages and disadvantages stated are too broad and sometimes overlap. Of course, it can depend on several factors: the targeted tissues; the loaded compounds; the type of administration; the final formulation; industrial scalability; among others. This way, this question aims at opening a debate to untangle and explore further the potentialities of each nanosystem and, more specifically, the (1) differential and (2) more specific applicabilities of each one towards the right final choice for the preconized biomedical application. Personal experiences and opinions are deeply welcomed!