 The field of precision oncology has been revolutionized by next-generation sequencing technologies and large-scale tumor molecular profiling programs, leading to the development of biomarker-matching therapies with significant survival benefits in several cancer types. However, healthcare professionals face challenges in interpreting and translating comprehensive genomic analyses, which require novel molecular characterization strategies beyond tumor DNA sequencing, such as transcriptomics, immunofenotyping, epigenetic profiling, and single-cell analyses. Liquid biopsies also provide potential applications for evaluating blood-based biomarkers like circulating tumor cells and circulating euclidic acids. Lessons learned from existing limitations of genotype-derived therapies can expand precision medicine beyond genomics. This article was authored by you and I'm alone, Marco Lever, Peter J. B. Sabatini, and others.