The past fifty years have seen a surge in the use of materials for clinical application, but in order to understand and exploit their full potential, the scientific complexity at both sides of the interface—the material on the one hand and the living organism on the other hand—needs to be considered. Technologies such as combinatorial chemistry, recombinant DNA as well as computational multi-scale methods can generate libraries with a very large number of material properties whereas on the other side, the body will respond to them depending on the biological context. Typically, biological systems are investigated using both holistic and reductionist approaches such as whole genome expression profiling, systems biology and high throughput genetic or compound screening, as already seen, for example, in pharmacology and genetics. The field of biomaterials research is only beginning to develop and adopt these approaches, an effort which we refer to as “materiomics”. In this review, we describe the current status of the field, and its past and future impact on the biomedical sciences. We outline how materiomics sets the stage for a transformative change in the approach to biomaterials research to enable the design of tailored and functional materials for a variety of properties in fields as diverse as tissue engineering, disease diagnosis and de novo materials design, by combining powerful computational modelling and screening with advanced experimental techniques.