Immunotherapy　has　emerged　as　a　novel　cancer　treatment　over　the　last　decade,　however,　efficacious　responses　to　mono-immunotherapy　have　only　been　achieved　in　a　relatively　small　portion　of　patients　whereas　combinational　immunotherapies　often　lead　to　concurrent　side　effects.　It　has　been　proved　that　the　tumor　microenvironment　(TME)　is　responsible　for　tumor　immune　escape　and　the　ultimate　treatment　failure.　Recently,　there　has　been　remarkable　progress　in　both　the　understanding　of　the　TME　and　the　applications　of　nanotechnological　strategies,　and　reviewing　the　emerging　immune-regulatory　nanosystems　may　provide　valuable　information　for　specifically　modulating　the　TME　at　different　immune　stages.　In　this　review,　we　focus　on　comprehending　the　recently-proposed　T-cell-based　tumor　classification　and　identifying　the　most　promising　targets　for　different　tumor　phenotypes,　and　then　summarizing　the　nanotechnological　strategies　to　best　target　corresponding　immune-related　factors.　For　future　precise　personalized　immunotherapy,　tailor-made　TME　modulation　strategies　conducted　by　well-designed　nanosystems　to　alleviate　the　suppressive　TME　and　then　promote　anti-tumor　immune　responses　will　significantly　benefit　the　clinical　outcomes　of　cancer　patients.　©　2021　IOP　Publishing　Ltd.