COSMIC-3D is a comprehensive integration of cancer mutations with protein structure across the human genome and structural proteome, seeking to support the identification and characterisation of protein targets for novel drug design in precision oncology. As an interactive system to explore cancer mutations in three-dimensions, COSMIC-3D is designed to enable a greater understanding of the functional impact of mutations, generate new hypotheses on which mutations are cancer drivers, and provide new opportunities for addressing these mutations pharmaceutically. This combination of genetics, structural proteomics, and drug development, can be best described as “mutation-guided drug design”.