Effectiveness of nanomedicines in cancer therapy is limited in part by inadequate delivery and transport in tumor interstitium. This article reviews the experimental approaches to improve nanomedicine delivery and transport in solid tumors. These approaches include tumor vasculature normalization, interstitial fluid pressure modulation, enzymatic extracellular matrix degradation, and apoptosis-inducing tumor priming technology. We advocate the latter approach due to its ease and practicality (accomplished with standard-of-care chemotherapy, such as paclitaxel) and tumor selectivity. Examples of applying tumor priming to deliver nanomedicines and to design drug/RNAi-loaded carriers are discussed.