Non-selectivity and dose-dependent side effects of doxorubicin (DOX), particularly cardio-toxicology as well as multidrug resistance in various tumor cells, have increased the demand for novel formulations with suitable efficiency and safety. Microformulations and nanoformulations have been shown to have satisfactory responses compared with that of conventional formulations. In this review, recent advances alongside the advantages and disadvantages of microformulations and nanoformulations are discussed. Doxil and Caelyx (PEGylated forms) as well as Myocet (non-PEGylated form) are presented as approved liposomal forms by the U.S. Food and Drug Administration to increase blood circulation half-life of DOX. Liposomes, micelles, hydrogels, lipid nanoparticles (NPs), polymeric NPs, polymersomes, metal/metal oxide NPs, mesoporous silica NPs, carbon-based NPs, and quantum dots are all major carriers for DOX and discussed accordingly. Considering all extracellular and intracellular conditions of cancer cells is an indispensable affair to obtain promising DOX carriers. Lack of a comprehensive related to drug-resistance cancer cells particularly in metastasis stages is an important hindrance to get acceptable results. Understanding of the drug resistance mechanisms in cancers cells particularly, in metastasis stages, is a critical factor to prepare efficient formulations.