In this review article, we describe the different nano-platforms developed in our laboratory at Northeastern University in Boston, MA for the targeted delivery of drugs and genes. Special emphasis is placed on nano-platforms that offer opportunities for multi-functionalization to allow for targeted stimuli-responsive and/or simultaneous strategic delivery of multiple drugs, genes, as well as the combination of therapeutic systems with image contrast enhancers. Polymeric and lipid-based nanocarriers can provide versatile platforms for the delivery of multiple pharmacological agents, specifically to enhance therapeutic effect and overcome drug resistance in cancer. In addition, polymeric nanoparticles and nanoparticles-in-microsphere oral system (NiMOS) are useful for systemic and oral gene therapy, respectively.