Gynecologic cancers are the cancers that originate in different reproductive organs of a woman. They are common between the age of 30 and 75 years. The major aggressive gynecologic cancers include cervical, ovarian, and endometrial cancers. Every type of gynecologic cancers are having distinctive signs, symptoms, and risk factors as well as various strategies for avoiding the disease conditions. All women are at threat for these cancers, and the danger increases with age and lifestyle activities. Chemotherapy is the first-line treatment option for major gynecologic cancers. However, the most common risk factor for major gynecologic cancers is the development of drug resistance to first-line therapeutic management/strategies. Noncoding RNAs are nonprotein coding transcripts which are differentially expressed among the malignant and benign tumors of gynecologic cancers as well as normal tissues. Deregulated expression of noncoding RNAs promotes or suppresses cancer initiation or progression as well as drug resistance. In addition, drug efflux mechanisms and their signaling mechanisms are also responsible for drug resistance in gynecologic cancers. This chapter attempts to describe the findings and drug resistance mechanisms with special reference to noncoding RNAs and drug efflux mechanisms in three aggressive gynecologic cancers of women.