Gynecologic malignancies have high incidence rates both nationally and internationally, and cervical, endometrial, and ovarian cancers account for high mortality rates worldwide. Significant research is ongoing to develop targeted therapies to address unmet needs in the field and improve patient outcomes. As tumors mutate and progress through traditional lines of treatment, new therapies must be developed to overcome resistance and target cancer-specific receptors and mutations. Recent advances in the development of immunotherapy and antibody-drug conjugates have resulted in compelling and clinically meaningful results in cervical, endometrial, and ovarian cancers. In the last decade, several immunotherapy agents have received FDA approval or NCCN guideline recommendation for the treatment of gynecologic malignancies, including dostarlimab for advanced or recurrent endometrial cancer and pembrolizumab for advanced or recurrent cervical and endometrial cancers. Several other immunotherapeutic agents are under active investigation. Development of antibody-drug conjugates including tisotumab vedotin in cervical cancer, mirvetuximab soravtansine in ovarian cancer, and trastuzumab deruxtecan in multiple gynecologic cancers has translated into exciting efficacy signals, prompting full drug approvals and additional investigation. This article aims to review recent novel advances in targeted treatments for gynecologic malignancies, highlighting the trials and data underlying these novel interventions.