The fields of biosensing and nanomedicine have recently witnessed an explosion of interest and progress in the design and study of plasmonic Au nanostructures (p-AuNSs) or metamaterials geared towards a broad range of biological and biomedical applications. Due to their tunable and versatile plasmonic properties, such artificially engineered p-AuNSs and materials have the potential to push biosensor sensitivity towards the single-molecule detection limit, enabling new bioimaging modalities and new analytical techniques and tools capable of single-molecule detection, analysis and manipulation, and to revolutionize the diagnosis and treatment of many diseases, including cancers. This report summarizes and highlights recent major advances in the emerging field of bioapplication-oriented engineering of p-AuNSs and hybrids, focusing on design considerations and ways to carry them out. A brief overview of the optical properties of p-AuNSs is introduced, and then the importance of plasmonic engineering and future promising research directions and challenges in the field are discussed.