The war on cancer remains a major challenge as one of the hurdles for additional progress is the complexity of the mechanisms underlying the disease. Cutting-edge technologies and computing tools have led to whole genome sequencing as well as an integrated and inclusive omic approach of cancers with accurate molecular tumors' signatures through impressive progress in the field of Next Generation Sequencing (NGS). Genomic data may foster strategies for new drug development in addition to a better understanding of cancer genesis, opening a new era in oncology clinical practice. This review discusses the development of genomics approaches in cancer research and its perspectives for precision medicine, as well as clinical implications and remaining challenges.