The article reviews the design principles and criteria for engineering multifunctional quantum dots (QDs) for bioimaging, detection, and drug delivery. QDs, semiconductor nanoparticles with unique photo-physical properties, have become a dominant class of imaging probes and platforms for multifunctional nanodevice engineering. The review outlines the general and application-specific design principles, emphasizing the importance of controlling QD size, surface chemistry, and bio-functionality. It discusses the challenges and advancements in QD synthesis, surface passivation, and bio-functionalization, highlighting the need for compact, stable, and biocompatible probes. The article also explores the use of QDs in molecular pathology, real-time monitoring of dynamic molecular processes, and their potential in clinical diagnostics and therapeutics. The future directions of QD-focused bionanotechnology research are discussed, focusing on multiplexed quantitative molecular profiling and the development of more advanced QD-based tools for biomedical applications.The article reviews the design principles and criteria for engineering multifunctional quantum dots (QDs) for bioimaging, detection, and drug delivery. QDs, semiconductor nanoparticles with unique photo-physical properties, have become a dominant class of imaging probes and platforms for multifunctional nanodevice engineering. The review outlines the general and application-specific design principles, emphasizing the importance of controlling QD size, surface chemistry, and bio-functionality. It discusses the challenges and advancements in QD synthesis, surface passivation, and bio-functionalization, highlighting the need for compact, stable, and biocompatible probes. The article also explores the use of QDs in molecular pathology, real-time monitoring of dynamic molecular processes, and their potential in clinical diagnostics and therapeutics. The future directions of QD-focused bionanotechnology research are discussed, focusing on multiplexed quantitative molecular profiling and the development of more advanced QD-based tools for biomedical applications.