Cancer, a complex series of diseased conditions, contributes to major health problem and is the leading cause of death across the world. Lately, with the advent of improved diagnostics and imaging techniques, and newer advanced oral chemotherapeutic; millions of cancer affected people are being able to lengthen their life span. Despite of all the challenges associated with an active chemotherapeutic molecule like microenvironment and the intestinal barrier of the gastrointestinal tract etc., The oral delivery remains the most acceptable route of drug administration. In this regard, nanotechnology has played significant role in the counteracting the challenges offered by newly developed molecules and aiding in improving their bioavailability and targetability to the tumor site while administering through the oral route. Several literature instances, document the usage of nanostructured drug delivery systems such as lipid-based, polymer-based or metallic nanomaterials to improve the efficacy of chemotherapy. Besides, site specific targeted surface modified drug delivery system designed to deliver the active molecule has opened up to the newer avenues of nanotechnology. However, the issue of potential toxicity allied with nanotechnology cannot be compromised and thus, needs certain ethical regulations and guidelines. The various in vitro models have been developed to evaluate the in-vitro toxicity profile which can be further correlated with the in-vivo model. Thus, this review provides a summarized account the various aspects related to role of nanotechnology in cancer therapy and various related issues thereof; that must be triumphed over to apprehend its full promise.