Over the past few decades significant advances have been made in the development of nanopharmaceuticals (including phospholipid and polymer-based therapeutics) against cancer. There is still, however, room for improvement. Today, many researchers are focusing on the development of innovative approaches to selectively deliver drugs to solid tumors, while minimizing insult to healthy tissues. Unfortunately, the majority of these efforts are confronted by physiological barriers that reduce the clinical dose required to effectively manage the disease state. In an effort to develop promising nanopharmaceutical products of the future, we review the most important problems facing drug delivery experts today. We discuss here, the physiological role of solid tumors in delivery and transport of nanopharmaceutical products. The nature of tumors in terms of their unique anatomical structure and functions is also discussed. Finally, an overview of ways to overcome physiological barrier functions and exploit tumor pathogenesis for therapeutic gain is provided.