Laser keyhole welding of dissimilar metals has been simulated to study the effect of welding strategies (laser beam displacements and tilts) and combination of metals to be welded on final quality of the joints. Molten pool geometry and welding penetration have been studied but special attention has been paid to final joint material properties, such as microstructure/phases and hardness, and especially to the residual stress state because it greatly conditions the service life of laser-welded components. For a fixed strategy (laser beam perpendicular to the joint) austenitic to carbon steel laser welding leads to residual stresses at the joint area very similar to those obtained in austenitic to martensitic steel welding, but welding of steel to Inconel 718 results in steeper residual stress gradients and higher area at the joint with detrimental tensile stresses. Therefore, when the difference in thermo-mechanical properties of the metals to be welded is higher, the stress state generated is more detrimental for the service life of the component, and consequently more relevant is the optimization of welding strategy. In laser keyhole welding of austenitic to martensitic stainless steel and austenitic to carbon steel, the optimum welding strategy is displacing the laser beam 1 mm toward the austenitic steel. In the case of austenitic steel to Inconel welding, the optimum welding strategy consists in setting the heat source tilted 45 deg and moved 2 mm toward the austenitic steel.