Next-generation sequencing (NGS) technologies and data have revolutionized cancer research and are increasingly being deployed to guide clinicians in treatment decision-making. NGS technologies have allowed us to take an “omics” approach to cancer in order to reveal genomic, transcriptomic, and epigenomic landscapes of individual malignancies. Integrative multi-platform analyses are increasingly used in large-scale projects that aim to fully characterize individual tumours as well as general cancer types and subtypes. In this review, we examine how NGS technologies in particular have contributed to “omics” approaches in cancer research, allowing for large-scale integrative analyses that consider hundreds of tumour samples. These types of studies have provided us with an unprecedented wealth of information, providing the background knowledge needed to make small-scale (including “N of 1”) studies informative and relevant. We also take a look at emerging opportunities provided by NGS and state-of-the-art third-generation sequencing technologies, particularly in the context of translational research. Cancer research and care are currently poised to experience significant progress catalyzed by accessible sequencing technologies that will benefit both clinical- and research-based efforts.