Cancer　immunotherapy　has　achieved　promising　clinical　progress　over　the　recent　years　for　its　potential　to　treat　metastatic　tumors　and　inhibit　their　recurrences　effectively.　However,　low　patient　response　rates　and　dose-limiting　toxicity　remain　as　major　dilemmas　for　immunotherapy.　Stimuli-responsive　nanoparticles　(srNPs)　combined　with　immunotherapy　offer　the　possibility　to　amplify　anti-tumor　immune　responses,　where　the　weak　acidity,　high　concentration　of　glutathione,　overexpressions　of　enzymes,　and　reactive　oxygen　species,　and　external　stimuli　in　tumors　act　as　triggers　for　controlled　drug　release.　This　review　highlights　the　design　of　srNPs　based　on　tumor　microenvironment　and/or　external　stimuli　to　combine　with　different　anti-tumor　drugs,　especially　the　immunoregulatory　agents,　which　eventually　realize　synergistic　immunotherapy　of　malignant　primary　or　metastatic　tumors　and　acquire　a　long-term　immune　memory　to　prevent　tumor　recurrence.　The　authors　hope　that　this　review　can　provide　theoretical　guidance　for　the　construction　and　clinical　transformation　of　smart　srNPs　for　controlled　drug　delivery　in　synergistic　cancer　immunotherapy.　©　2021　The　Authors.　Advanced　Science　published　by　Wiley-VCH　GmbH.