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The heterogeneity of the tumor microenvironment is like a \u201csea fog\u201d that hinders precision medicine. This makes it difficult for traditional active targeting that relies on natural targets to achieve precise delivery. For this difficulty, this review summarizes the constraints of tumor microenvironment heterogeneity on nanomaterials in terms of time and space. Pre\u2010targeting strategies enhance delivery efficiency by constructing an \u201cartificial lighthouse.\u201d According to the source of the target and the mode of specific binding, this review divides pre\u2010targeting strategies into two categories: biomolecular recognition\u2010mediated and bioorthogonal click chemistry\u2010mediated. On this basis, this review comprehensively introduces recent progress in pre\u2010targeting\u2010enabled nanomedicine in body fluid\u2010based detection, in vivo imaging, and multi\u2010therapies. Furthermore, this review is the first to summarize the synergistic mechanisms of pre\u2010targeting with prodrugs, insitu self\u2010assembly, and dual\u2010targeting strategies. This review systematically summarizes the complete framework of pre\u2010targeting strategies, from mechanisms and classifications to applications and expansions. It aims to provide inspiration for the development of nanomedicine in the field of oncology for effective cancer diagnosis and treatment.<\/jats:p>","DOI":"10.1002\/mabi.70262","type":"journal-article","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T19:53:37Z","timestamp":1789847617000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["\u201cArtificial Lighthouse\u201d Overcomes Tumor Microenvironment Heterogeneity's \u201cSea Fog\u201d: Pre\u2010Targeted Strategy\u2010Mediated Nanomedicine Enables Tumor Body Fluid Detection, In Vivo Imaging, and Multitherapy Treatment"],"prefix":"10.1002","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6244-4178","authenticated-orcid":false,"given":"Yinuo","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Toxicology and Sanitary Chemistry School of Public Health Capital Medical University  Beijing People's Republic of 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