Development of novel strategies to overcome chemoresistance is central goal in ovarian cancer research. Natural history of the cancer development and progression is being reconstructed by genomic datasets to understand the evolutionary pattern and direction. Recent studies suggest that intra-tumor heterogeneity (ITH) is the main cause of treatment failure by chemoresistance in many types of cancers including ovarian cancer. ITH increases the fitness of tumor to adapt to incompatible microenvironment. Understanding ITH in relation to the evolutionary pattern may result in the development of the innovative approach based on individual variability in the genetic, environment, and life style. Thus, we can reach the new big stage conquering the cancer. In this review, we will discuss the recent advances in understanding ovarian cancer biology through the use of next generation sequencing (NGS) and highlight areas of recent progress to improve precision medicine in ovarian cancer.