Nanotechnology offers new strategies for minimally invasive and localized approaches to diagnose and treat diseases. Recently, nanoparticles have been explored in a range of applications, including as drug delivery vehicles, imaging probes, and therapeutic agents. Although increased therapeutic efficacy has been realized, direct visualization of how engineered nanoparticles interact with specific organelles or cellular components has seen limited attention. Such interactions will have implications for fundamentals in cancer biology as well as in the design of translational therapeutic agents. This talk will describe how drug-loaded gold nanostars can behave as multi-spectral optical probes for interrogating how therapeutic nanoconstructs affect cancer cells at the nanoscale. We will focus on model cancer cell systems that can be used to visualize how gold nanostar nanoconstructs target cells, rotate on the plasma membrane, are endocytosed, and are trafficked intracellularly. We will also discuss mechanisms of cell death associated with these unique therapeutic nanoconstructs.