Enrichment-detection integrated biosensors for exosome profiling have shown great potential in noninvasive diagnosis and point-of-care testing with the advantage of multifunctions. This Feature focuses on the enrichment-detection integrated exosome profiling biosensors emphasizing (i) the underlying working fundamentals of these sorts of biosensors, (ii) four advanced strategies developed for exosome analysis, and (iii) future outlook and present challenges of exosome profiling systems.