Cancer is a dynamic disease characterized by its heterogeneous nature. This heterogeneity results in critical problems that interfere with the eradication of cancer tumors such as multidrug resistance, drug efflux capacity, narrow therapeutic window, and undesired side effects. Nanomedicine has introduced new platforms for drug delivery to enhance therapeutic efficiency of anticancer drugs. In addition to drug delivery, nanocarriers such as liposomes, carbon nanotubes, quantum dots, polymeric nanoparticles, dendrimers, and metallic nanoparticles can be designed for detection, diagnosis, and treatment. Recent studies support the idea that a combination of two or more nanoparticle-mediated therapies can result in a synergistic therapeutic outcome to improve current cancer treatments. In this progress report, recent advances in nanoparticles-based combination therapies are discussed. A brief overview of the complexity of cancer tumor's microenvironment is presented, followed by discussion of combinatorial therapies categorized based on chemotherapeutic agents, nucleic acid or therapeutic proteins, energy-based therapies and imaging techniques for theranostic application. Different nanotechnological platforms are developed for combination therapy as tools with a great potential to tackle the most critical issues of current cancer treatments. A deeper understanding of these nanotechnologies and their possible long-term effects in biological systems is needed for further clinical translation.