For decades, cancer treatment was largely organ-based, relying on conventional modalities such as surgery. Advances in molecular biology and biotechnology have profoundly transformed this paradigm by revealing shared oncogenic mechanisms across diverse tumor types. This shift has enabled the emergence of precision oncology and tumor-agnostic therapies, which target specific molecular alterations regardless of tissue of origin. This paper reviews these developments, drawing in part on discussions from the 2025 Journées nationales d’actualités en oncologie organized by the French Society for Oncology Pharmacy (SFPO) and by highlighting the growing roles of Hospital Oncology Pharmacists (HOP)s. Several biomarkers have led to FDA-approved tumor-agnostic therapies, including MSI-H/dMMR status, NTRK and RET fusions, BRAFV600E mutations, and HER2 overexpression. Therapeutic advances include combined BRAF and MEK inhibition for BRAF V600E – mutated cancers and HER2-directed antibody – drug conjugates with indications beyond breast and gastric tumors. Despite these successes, significant challenges remain. Access to comprehensive molecular testing is limited in some settings, while cancer biology is influenced not only by genetic alterations but also by tissue context, co-mutations, and the tumor microenvironment. Integrating clinical and molecular data requires robust bioinformatics infrastructure, and communicating complex molecular results to patients remains challenging. HOPs are central to overcoming these barriers. Through participation in innovative clinical trials, molecular tumor boards, and early-access programs, they support the implementation of precision oncology and help ensure equitable access to tumor-agnostic therapies. Clinical pharmacy activities must also be provided for patients receiving these tumor-agnostic treatments in order to optimize their care through the assessment of drug-drug interactions, monitoring of adverse effects, and of treatment adherence.