Additive manufacturing technology enables novel processing capabilities for multi-material metallic structures, with the possibility of gradual changes of chemical composition throughout a component. However, with a gradual change in chemical composition, material design and process control is challenging. When transitioning from one composition to another, unwanted intermetallic phases are prone to form, and the processing parameters change with the composition of the component. A framework is developed to control the intermetallic phase formation, accelerate material design, and support additive manufacturing process optimization. The framework includes thermodynamic calculations to predict thermal and kinetic properties, experimental validation by arc melting, finite element process simulation, and directed energy deposition experiments. The framework is demonstrated on a multi-material specimen made up of 316L stainless steel, Inconel 625 and aluminium alloy 4043. The framework can be extended to different material systems and processes to be used in a wide range of applications.