Genomic instability is one of the main properties of tumour development, promoting first the acquisition of genetic alterations and thus carcinogenesis. Then, the chronic and anarchic proliferation of cancer cells also supports and contributes to this instability allowing a continuous evolution of the tumour. The accumulation of mutations resulting from that instability contributes to tumour heterogeneity that occurs in a specific environment. The resulting diversity of oncogenic drivers further complicates the characterization of the origin of cancer cells dysfunction and consequently therapeutic decision. However, the consideration of the molecular context in oncology has initiated the development of targeted therapies. Based on the concept of oncogene addiction and synthetic lethality, these new drugs require the characterization and identification of specific tumour biomarkers. Targeted therapies have thus considerably optimized patient management, improving efficiency and quality of life while limiting the side effects observed with conventional chemotherapies. However, despite significant clinical benefits, some major limitations to their administration remain. The study of the current issues related to these new therapeutic molecules is becoming crucial for patient management towards an improvement of personalized medicine.