The utilization of innovative manufacturing technologies, such as wire arc additive manufacturing (WAAM), presents advantages in production of large, functional structures, reducing lead time and material consumption. However, to integrate WAAM parts into failure-critical aerospace applications, a comprehensive understanding of design factors influencing manufacturing quality is imperative. This thesis focuses on advancing simulation methodologies for WAAM, targeting the titanium alloy Ti-6Al-4V. The main objective is to improve simulation accuracy of process factors like residual stress and distortion, considering the layer-wise nature of the WAAM process itself. Additionally, to enhance the obtained quality of WAAM structures, a thorough investigation into fatigue strength and tailoring of WAAM-process applicable assessment methodologies is conducted. The development of the enhanced simulation methodology involves an in-depth exploration of material intrinsic WAAM properties, such as creep and strain rate. Comprehensive material tests, including tensile, creep, and low-cycle fatigue experiments, are conducted to study both the complex creep and the cyclic elasto viscoplastic behavior of Ti-6Al-4V WAAM and titanium substrate. Implementable material models are rated, leading to the integration of an advanced Norton-Bailey creep and cyclic Chaboche model. Validation through experimental manufacturing of complex representative structures reveals a substantial improvement over conventional approaches, for example, reducing mean error of distortion compared to experimental measurements from 60% to 6%. In regard to the fatigue strength assessment of WAAM structures, this thesis focuses on understanding the impact of process-induced porosity. Detailed experimental characterizations, including fatigue and low-cycle fatigue tests, coupled with fractographic and microstructural investigations, are conducted. As both surface and inner pores were found on the fractured surfaces, a probabilistic stress-intensity equivalent transformation approach is developed. Summing up, this work presents an engineering-feasible simulation methodology for the thermo-mechanical simulation of Ti-6Al-4V WAAM, providing accurate results of residual stress, distortion, and temperature distribution for each WAAM layer. Furthermore, a probabilistic fatigue assessment concept is introduced to assess for the presence of defects in WAAM material. These advancements enhance the understanding of the WAAM process settings and open avenues for the application of WAAM parts in dedicated aerospace applications.