This study aims to propose a thorough experimental methodology to assess the mechanical quality of dissimilar joints. This comprehensive approach investigates the fatigue behavior by exploiting the thermographic method, accompanying and correlating the results with information obtained from extensive measurements of residual stresses and detailed evaluation of fracture surfaces. The integration of the information obtained by this hybrid approach allows for a deeper understanding in terms of fatigue behavior even in complicated situations as those represented by dissimilar welded joints. A complex laser-welded Ti6Al4V/Inconel 625 dissimilar joint, obtained using intermediate inserts of Vanadium and AISI 304, was considered as case study. The residual stresses, both longitudinal and transverse to the weld beads, were measured on surface by means of X-ray diffraction, whereas, for in-depth measurements, the multiple-cut contour method was implemented to determine full 2D maps of longitudinal residual stresses with the first cut, and transverse stresses in the Vanadium insert with the second cut. In the investigation of longitudinal residual stresses, the area mostly affected by harmful tensile residual stresses is the weld between the stainless steel and Vanadium, where the maximum value of about 560 MPa is reached; the analysis of transverse residual stresses highlighted a maximum value of 350 MPa at the core of the Vanadium insert. The fatigue behavior of the joints was investigated along with a detailed analysis of the fractured surfaces by scanning electron and confocal microscopes. The analysis of the fracture surfaces indicated that the failure modes are mainly related to the occurrence of defects on the crack path, especially at stress range higher than 200 MPa, for which a large number of pores cluster were detected. Nevertheless, the crack initiation is usually on the side of Vanadium. When the crack path deviates on the stainless-steel region, the fracture mode is brittle due to high residual stresses.