In　this　work,　we　proposed　nµPEF,　a　novel　pulse　configuration　combining　nanosecond　and　microsecond　pulses　(nµPEF),　to　enhance　tumor　ablation　in　irreversible　electroporation　(IRE)　for　oncological　therapy.　nµPEF　demonstrated　improved　efficacy　in　inducing　immunogenic　cell　death,　positioning　it　as　a　potential　candidate　for　next-generation　ablative　therapy.　However,　the　immune　response　elicited　by　nµPEF　alone　was　insufficient　to　effectively　suppress　distant　tumors.　To　address　this　limitation,　we　developed　PPR@CM-PD1,　a　genetically　engineered　nanovesicle.　PPR@CM-PD1　employed　a　polyethylene　glycol-polylactic　acid-glycolic　acid　(PEG-PLGA)　nanoparticle　encapsulating　the　immune　adjuvant　imiquimod　and　coated　with　a　genetically　engineered　cell　membrane　expressing　programmed　cell　death　protein　1　(PD1).　This　design　allowed　PPR@CM-PD1　to　target　both　the　innate　immune　system　through　toll-like　receptor　7　(TLR7)　agonism　and　the　adaptive　immune　system　through　programmed　cell　death　protein　1/programmed　cell　death-ligand　1　(PD1/PDL1)　checkpoint　blockade.　In　turn,　nµPEF　facilitated　intratumoral　infiltration　of　PPR@CM-PD1　by　modulating　the　tumor　stroma.　The　combination　of　nµPEF　and　PPR@CM-PD1　generated　a　potent　and　systemic　antitumor　immune　response,　resulting　in　remarkable　suppression　of　both　nµPEF-treated　and　untreated　distant　tumors　(abscopal　effects).　This　interdisciplinary　approach　presents　a　promising　perspective　for　oncotherapy　and　holds　great　potential　for　future　clinical　applications.　©　2023　Wiley-VCH　GmbH.