Purpose of Review: Triple-negative breast cancer (TNBC) is notoriously difficult to treat. Recent technological advances have led to the identification of novel targets and new approaches to treat this devastating disease. The aim of this review is to highlight therapeutic vulnerabilities of TNBC and discuss novel therapeutic strategies. Recent Findings: Interrogating the inherent heterogeneity and rich cellular and transcriptional diversity within TNBC has led to the discovery of vulnerabilities and actionable targets for therapeutic development. Characterization of the tumor immune environment, discovery of novel molecular targets, and identification of somatic alterations which confer sensitivity to DNA repair inhibitors are just a few examples. Summary: The key to developing effective strategies to treat TNBC is to exploit vulnerabilities using a multifaceted approach. The identification of actionable targets has led to numerous therapeutic advances for TNBC, resulting in substantial improvements in patient outcomes and quality of life.