The development of the next generation of Titanium alloys for high temperature applications is expected to involve a new paradigm in alloy development based on a synergistic coupling of experimental and modeling tools. This paper describes the application of a combinatorial approach to alloy development and database population employing graded alloys produced by laser deposition of elemental blends of powders. The focus of this study is the beta Ti alloy, Ti-15Mo-3Nb-3Al, often referred to as TIMETAL-21S. The objective is to explore the influence of substitutions in the alloying additions, such as Cr and V instead of Mo. Therefore, alloy variations of Ti-xMo-(15-x)Cr-3Nb-3Al and Ti-xMo-(15-x)V-3Nb-3Al, will be laser deposited from blends of elemental powders. These samples will be upset pressed, and subsequently iso-compositional tensile coupons will be machined, heat-treated, and mechanically tested. Additional testing of critical high temperature properties such as oxidation resistance will also be carried out. The eventual goal is to quantify the microstructural features as a function of the composition and heat treatment parameters using rigorous stereological procedures and build a microstructurally-based database linking to the measured mechanical and other properties. This database will be used to train and test neural-network models for predicting the property-microstructure relationships in these alloys and thus allow for the development of optimum compositions and microstructures with desired properties. An update on this research effort will be presented in this paper.