The unique combination of mechanical properties and the ability to be processed using injection molding techniques makes bulk metallic glasses (BMGs) excellent candidates for use in engnineering applications, especially in the medical device industry. Widespread use of BMGs is hindered by their inability to be joined to common engineering materials (ex. titanium) with standard fusion welding techniques (ex. laser welding). In this paper a definitive screening design experiment was performed to optimize a dissimilar Vitreloy 105 to grade 2 titanium laser weld. The optimized weld was then characterized using nanoindentation, scanning electron micrscopy, micro cantilever beam bending, and transmission electron microscopy. It was found that the optimized weld had lower hardness, a more uniform structure, and better performance than the baseline seam weld between the dissimilar materials. The microstructural and micromechanical characterization of the optimized joints showed variation in local mechanical properties that were correlated to chemistry and microstructure ranging from brittle fracture at low loads to ductility and toughness arising from shear band blunting. Not only did the optimized welding process confrim that Vitreloy 105 could be successfully laser joined to grade 2 titanium with properties acceptable for many applications, the investigation into the local structure and properties of the joint revealed the possibility of creating ductile metallic glass composites by controlling the chemistry and structure of the intermetalic zone while processing.