Precision medicine is transforming hematologic cancer care by tailoring treatments to individual patient profiles and moving beyond the traditional “one-size-fits-all” model. This review outlines foundational technologies, disease-specific advances, and emerging directions in precision hematology. The field is enabled by molecular profiling techniques, including next-generation sequencing (NGS), whole-exome sequencing (WES), and RNA sequencing (RNA-seq), as well as epigenomic and proteomic analyses. Complementary tools such as liquid biopsy and minimal residual disease (MRD) monitoring have improved diagnosis, risk stratification, and therapeutic decision making. We discuss major molecular targets and personalized strategies across hematologic malignancies: FLT3 and IDH1/2 in acute myeloid leukemia (AML); Philadelphia chromosome–positive and Ph-like subtypes in acute lymphoblastic leukemia (ALL); BCR-ABL1 in chronic myeloid leukemia (CML); TP53 and IGHV mutations in chronic lymphocytic leukemia (CLL); molecular subtypes and immune targets in diffuse large B-cell lymphoma (DLBCL) and other lymphomas; and B-cell maturation antigen (BCMA) in multiple myeloma. Despite significant progress, challenges remain, including high costs, disparities in access, a lack of standardization, and integration barriers in clinical practice. However, advances in single-cell sequencing, spatial transcriptomics, drug repurposing, immunotherapies, pan-cancer trials, precision prevention, and AI-guided algorithms offer promising avenues to refine treatment and improve outcomes. Overcoming these barriers will be critical for ensuring the equitable and widespread implementation of precision medicine in routine hematologic oncology care.

Non-small cell lung cancer (NSCLC) accounts for up to 85% of lung cancer cases, with activating EGFR mutations present in 10–15% of Western and up to 35% of Asian patients. EGFR tyrosine kinase inhibitors (TKIs) have transformed management, with first-line osimertinib demonstrating a median progression-free survival (PFS) of 18.9 months and overall survival (OS) of 38.6 months in the FLAURA trial. However, resistance inevitably develops, most commonly via T790M mutations (~50% of cases after first- and second-generation TKIs), and after osimertinib, through diverse mechanisms including C797S mutations, MET/HER2 amplification, and histologic transformation. Emerging strategies to overcome resistance include next-generation TKIs, combination targeted therapies, downstream pathway inhibitors, immunotherapy approaches, and antibody–drug conjugates. Understanding these mechanisms is critical for optimizing patient outcomes and guiding personalized therapeutic approaches. This review discusses current strategies to delay or overcome resistance and highlights emerging therapeutic avenues with the potential to reshape the management of EGFR-mutant NSCLC.