The present invention relates to targeted delivery systems for delivering therapeutic agents to tumor. The invention further relates to methods of delivering a therapeutic agent to a tumor for the prevention and treatment of cancer by killing tumor cells and tumor-associated endothelial cells. In particular, the present invention provides a tumor-targeted drug delivery system comprising a NGR-containing molecule linked to a delivery vehicle encapsulating a therapeutic agent, preferably a drug, such as a cytotoxic agent or a chemotherapeutic agent. Specifically, the delivery systems of the present invention are capable of delivering an increased amount of therapeutic agent to a tumor as compared to other delivery systems. In particular, the delivery systems of the present invention are capable of accumulating a higher amount of therapeutic agent in a tumor, or in the vicinity of a tumor cell or tumor-supporting cell, resulting in exposure of the tumor cell and tumor-associated endothelial cell to therapeutic levels of the agent for a longer period of time as compared to other delivery systems. The present invention also describes pharmaceutical compositions comprising the delivery systems of the present invention. The present invention further relates to a tumor treatment comprising an increased amount of therapeutic agent delivered by the system of the present invention as compared to other delivery systems. The delivery systems and pharmaceutical compositions can be administered to a subject, preferably a human, alone or in combination, sequentially or simultaneously, with other prophylactic or therapeutic agents and/or anti-cancer treatments.