Exosomes, as next-generation biomarkers, has great potential in tracking cancer progression. They face many detection limitations in cancer diagnosis. Plasmonic biosensors have attracted considerable attention at the forefront of exosome detection, due to their label-free, real-time, and high-sensitivity features. Their advantages in multiplex immunoassays of minimal liquid samples establish the leading position in various diagnostic studies. This review delineates the application principles of plasmonic sensing technologies, highlighting the importance of exosomes-based spectrum and image signals in disease diagnostics. It also introduces advancements in miniaturizing plasmonic biosensing platforms of exosomes, which can facilitate point-of-care testing for future healthcare. Nowadays, inspired by the surge of artificial intelligence (AI) for science and technology, more and more AI algorithms are being adopted to process the exosome spectrum and image data from plasmonic detection. Using representative algorithms of machine learning has become a mainstream trend in plasmonic biosensing research for exosome liquid biopsy. Typically, these algorithms process complex exosome datasets efficiently and establish powerful predictive models for precise diagnosis. This review further discusses critical strategies of AI algorithm selection in exosome-based diagnosis. Particularly, we categorize the AI algorithms into the interpretable and uninterpretable groups for exosome plasmonic detection applications. The interpretable AI enhances the transparency and reliability of diagnosis by elucidating the decision-making process, while the uninterpretable AI provides high diagnostic accuracy with robust data processing by a “black-box” working mode. We believe that AI will continue to promote significant progress of exosome plasmonic detection and mobile healthcare in the near future.