This article presents a comprehensive piece of research work focused on the development, validation and application of finite element modelling capability for the prediction and optimization of robotic keyhole plasma arc welding of Ti-6Al-4V thin structures. Experimental and computational investigations were carried out to characterize, develop, optimize and validate various aspects of the finite element modelling. The experimental investigations cover the determination of welding parameter envelopes using a robotic welding cell and the measurements of thermal history, distortion, residual stress and weld pool profile. The computational investigations include the development and validation of finite element models as well as the development and validation of a fully automated welding sequence optimization tool using a genetic algorithm approach. The work provides useful guidance and generic methodologies for optimum design of thin and complex lightweight structures and has formed a basis for the development of a framework on structural integrity assessment and component lifing of thin structures fabricated by welding. The optimization tool has significant potential to be conveniently modified to suit other optimization objectives and/or welding processes.