The article discusses the implications of cancer heterogeneity for targeted therapeutics. It highlights the increasing evidence that solid tumors can contain subpopulations of cells with distinct genomic alterations, a phenomenon known as intra-tumour heterogeneity. This heterogeneity has significant implications for cancer therapeutics and biomarker discovery, particularly in the context of targeted treatments. The authors review the current understanding of the processes that exacerbate intra-tumour heterogeneity, both iatrogenic and tumor-specific, and suggest how this knowledge can be integrated into future clinical practice and research efforts to optimize patient care and clinical outcomes. They also discuss the dynamic nature of tumor heterogeneity, its impact on drug resistance, and the challenges it poses for biomarker validation and personalized therapy. The article emphasizes the need for systematic approaches to studying molecular heterogeneity in cancer, including longitudinal analyses of tumor evolution over time, to better understand and address the complexities of cancer heterogeneity.The article discusses the implications of cancer heterogeneity for targeted therapeutics. It highlights the increasing evidence that solid tumors can contain subpopulations of cells with distinct genomic alterations, a phenomenon known as intra-tumour heterogeneity. This heterogeneity has significant implications for cancer therapeutics and biomarker discovery, particularly in the context of targeted treatments. The authors review the current understanding of the processes that exacerbate intra-tumour heterogeneity, both iatrogenic and tumor-specific, and suggest how this knowledge can be integrated into future clinical practice and research efforts to optimize patient care and clinical outcomes. They also discuss the dynamic nature of tumor heterogeneity, its impact on drug resistance, and the challenges it poses for biomarker validation and personalized therapy. The article emphasizes the need for systematic approaches to studying molecular heterogeneity in cancer, including longitudinal analyses of tumor evolution over time, to better understand and address the complexities of cancer heterogeneity.