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Two\u2010photon PDT (TP\u2010PDT) offers a powerful strategy by enabling near\u2010infrared excitation with deeper penetration, higher spatial precision, and reduced off\u2010target photodamage. In this context, metal complexes have emerged as particularly attractive TP PSs because their coordination frameworks allow precise control over spin\u2013orbit coupling, excited\u2010state dynamics, redox reactivity, and reactive oxygen species generation through both Type I and Type II pathways. Recent advances show that ligand engineering, photo\u2010decaging strategies, supramolecular design, and nanostructuring can substantially enhance two\u2010photon absorption, charge separation, radical generation, and therapeutic efficacy, especially in hypoxic tumors. This review overviews recent progress in two\u2010photon\u2010activatable metal complexes for PDT, highlighting design principles and therapeutic advances across ruthenium\u2010, iridium\u2010, platinum\u2010, and related metal\u2010based complexes. Particular emphasis is given to how coordination design governs photophysical properties, biological performance, and treatment outcomes. Current challenges and future opportunities for the clinical translation of these systems are also discussed.<\/jats:p>","DOI":"10.1002\/anie.2556404","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T16:16:49Z","timestamp":1783009009000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Recent Advances in Two\u2010Photon\u2010Activatable Metal Complexes for Photodynamic Therapy"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6721-890X","authenticated-orcid":false,"given":"Jinzhe","family":"Liang","sequence":"first","affiliation":[{"name":"College of Chemistry and Materials Science State Key Laboratory of Bioactive Molecules and Druggability Assessment Jinan University  Guangzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4153-5303","authenticated-orcid":false,"given":"Hui","family":"Chao","sequence":"additional","affiliation":[{"name":"College of Chemistry and Materials Science State Key Laboratory of Bioactive Molecules and Druggability Assessment Jinan University  Guangzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(25)01635\u20106"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568\u2010018\u20100004\u20109"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1424171112"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44222\u2010024\u201000196\u2010z"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41570\u2010024\u201000662\u20107"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.1c00381"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202408594"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751\u20101097.1985.tb01554.x"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.7b00180"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.2174\/187152008783961860"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202103978"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9CS00129H"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202112236"},{"key":"e_1_2_11_15_1","first-page":"378","article-title":"A Phase II\/III Clinical Study of Tin Ethyl Etiopurpurin (Purlytin)\u2010induced Photodynamic Therapy for the Treatment of Recurrent Cutaneous Metastatic Breast Cancer","volume":"4","author":"Mang T. 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