Bioinformatics is a key discipline for understanding the cancer genome and for the future of cancer therapeutics. Bioinformatics-based approaches have the ability to transform the vast amount of biological data into comprehensive models that provide a deep understanding of cancer disease and the complex genotype-phenotype relationships needed to identify molecular cancer-driving alterations and novel therapeutic targets. The CNIO Bioinformatics Unit (BU) has developed new in-house computational methodologies and bioinformatics tools to enable the integration of biological and clinical data to achieve genome analysis in cancer patients’ data, identifying new biomarkers and drug response mechanisms. Its final goal is to implement their methodologies in the Health System.