In this work, we present an overview of the development and application of surface‐enhanced Raman scattering (SERS) and plasmonic nanoplatforms developed in our laboratory in recent years. We have developed a wide variety of plasmonics‐active substrates and nanoparticle‐based sensing platforms including inverse molecular sentinels (iMS) utilizing gold nanostars (AuNS) and nanorattle DNA sensors (NR). These platforms have been used for a wide variety of applications, such as monitoring genomic biomarkers in plants for renewable bioenergy research, point‐of‐care diagnostics of infectious diseases (dengue and malaria), and detection of cancer biomarkers for gastrointestinal and head and neck cancers. Applications of plasmonic AuNS in bioimaging, photothermal therapy (PTT), and immunotherapy are also presented. An interesting advance was the development of AuNS‐mediated PTT in combination with immunotherapy, a method referred to as Synergistic Immuno Photothermal Nanotherapy (SYMPHONY), which broadens and significantly enhances the efficacy of immunotherapy. This review highlights various applications of the unique plasmonics‐enabled sensing and therapeutic nanotechnologies that contribute to the lasting legacy of the discovery of SERS.