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This review highlights recent first\u2010line standard of care treatment options and explores biomarker\u2010driven strategies, particularly homologous recombination deficiency for personalized treatment selection. We emphasize how the adoption of tumor next\u2010generation sequencing is shaping precision therapy, including tumor\u2010agnostic targets such as NRG1 fusions and BRAF alterations in KRAS wild\u2010type tumors. Advances in KRAS inhibitors, PROTACs, tumor treating fields, and PRMT5 inhibitors for MTAP\u2010deleted tumors are rapidly expanding potential treatment options for patients. Emerging immunotherapies targeting Claudin18.2 and CXCR4 offer hope to overcome tumor resistance. Together, these strategies underscore the promise of molecular stratification, synthetic lethality, and novel targets to improve pancreatic cancer survival.<\/jats:p>","DOI":"10.1111\/jgh.70353","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T04:48:48Z","timestamp":1774414128000},"page":"1427-1435","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Systemic Therapy for Advanced Pancreatic Cancer in 2025: Current Standard\u2010of\u2010Care and Emerging Therapeutic Strategies"],"prefix":"10.1111","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3928-1471","authenticated-orcid":false,"given":"Gerry\u00a0Gin\u00a0Wai","family":"Kwok","sequence":"first","affiliation":[{"name":"Department of Medicine Queen Mary Hospital, University of Hong Kong  Hong 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