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Here, we proposed an effective synergistic strategy with intelligent biomaterials to overcome the limitation of conventional cryo\u2010thermal therapy that requires two separate devices, integrating cryo\u2010thermal ablation, mechanical destruction, and drug release to improve therapeutic efficacy. A sodium alginate (SA) modified iron\u2010containing liquid metal microdroplet (FLMM@DOX@SA) was fabricated with diverse intelligent merits under stimulation. Under cooling, FLMM@SA would go through a multi\u2010phase transition process and present a unique \u201cbomb\u2010explosion\u2010like\u201d behavior, leading to fierce mechanical destruction (more than 6.3\u00a0MPa) to surrounding ice crystals. Then, FLMM@SA was demonstrated as a powerful magnetocaloric agent when subject to an alternating magnetic field. In addition, this intelligent biomaterial exhibited stimulus\u2010enhanced drug release across multiple cues, including cryo\u2010stimulation, magnetothermal activation, and pH changes, thereby driving synergistic antitumor efficacy with the highest fraction of necrotic cells. The mechano\u2010thermal\u2010chemo\u2010freezing synergistic therapy further verified the effective destructive performance with robust tumor growth suppression and a 100% animal survival rate. Collectively, this work highlights the integration of intelligent biomaterials into cryoablation, thereby forging a novel modality for highly effective combination therapy.<\/jats:p>","DOI":"10.1002\/smll.76152","type":"journal-article","created":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T16:09:16Z","timestamp":1791734956000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Liquid Metal Multi\u2010Functional Droplets Enabled High\u2010Performance Tumor Therapy With Four Synergistic Mechano\u2010Thermal\u2010Chemo\u2010Freezing Effects"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0088-5203","authenticated-orcid":false,"given":"Yi","family":"Liu","sequence":"first","affiliation":[{"name":"School of Engineering Medicine School of Biological Science and Medical Engineering Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education Beihang University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Engineering Medicine School of Biological Science and Medical Engineering Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education Beihang University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiani","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Engineering Medicine School of Biological Science and Medical Engineering Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education Beihang University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2392-2926","authenticated-orcid":false,"given":"Xiaolei","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Engineering Medicine School of Biological Science and Medical Engineering Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education Beihang University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Xiao","sequence":"additional","affiliation":[{"name":"Hygea Medical Technology Co., Ltd.  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