Advancing clinical and nonclinical diagnostic technologies is particularly crucial for improved preparedness for the next pandemic and other global healthcare challenges. To this end, marrying advanced microscopic imaging with chip‐scale bioanalytical systems provides fresh modalities by analyzing signals of transmitted, reflected, or scattered light waves. This review brings clarity to the latest progress of refractometric imaging and biodetections on a chip, in which interferences and resonances as cornerstones of optics and plasmonics are breaking new ground. A vast range of nanophotonic and plasmonic transducers are discussed, ranging from planar films, nanoarrays, and waveguiding resonators to holistic designs. The augmented bioanalyses cover immunoassays, single‐molecule analysis, and motion tracking of bacterial pathogens and cells. Compared to single‐point spectroscopic measurements, imaging‐empowered approaches are rapidly evolving with greatly promoted signal‐noise ratio, spatial‐temporal resolutions, multiplexability, and throughput, which can be accomplished in a compact cradle system with minimized bulky components in a spectrometer‐free manner. Besides, advances in machine learning technologies applied for data analytics and transducer designs are highlighted. All in all, there are unlimited opportunities for new optical structures, principles, and ways of data retrieval to tap in, which will raise technological impacts on unveiling fundamental issues in life science and advancing global healthcare technologies.