Due to the lack of early symptoms and difficulty of accurate diagnosis, ovarian cancer is the most lethal gynecological cancer faced by women. First-line therapy includes a combination of tumor resection surgery and chemotherapy regimen. However, treatment becomes more complex upon recurrence due to development of drug resistance. Drug resistance has been linked to many mechanisms, including efflux transporters, apoptosis dysregulation, autophagy, cancer stem cells, epigenetics, and the epithelial-mesenchymal transition. Thus, developing and choosing effective therapies is exceptionally complex. There is a need for increased specificity and efficacy in therapies for drug-resistant ovarian cancer, and research in targeted nanoparticle delivery systems aims to fulfill this challenge. Although recent research has focused on targeted nanoparticle-based therapies, few of these therapies have been clinically translated. In this review, non-viral nanoparticle delivery systems developed to overcome drug-resistance in ovarian cancer were analyzed, including their structural components, surface modifications, and drug-resistance targeted mechanisms.Copyright © 2020. Published by Elsevier Inc.