Recently, laser welding has become a leading industrial joining process. Mainly because it has become highly automated using sophisticated robotic systems. However, to make effective use of automated laser welding it is essential to have a high degree of confidence in predicting the welding outcome. To achieve a desired weld quality, the weldments are normally examined and related to the weld input parameters. This input-output relationship can be in the form of mathematical models that can be programmed and fed to the robotic control system. This work aims to introduce experimentally based mathematical models developed by applying Response Surface Methodology (RSM) using Design-Expert software V7 to relate the residual stress distribution, weld bead parameters, mechanical properties and operating cost to the laser welding input parameters, namely: laser power, welding speed and focal point position. Also, the desirability approach was used in conjunction with RSM to find out the optimal combination of the welding parameters to achieve the required weld quality. In addition to this, microstructural investigation of the welded joints was carried out to study the effect of varying the welding conditions on the microstructure of the Weld zone (WZ) and Heat affected zone (HAZ). Common materials were investigated in this work (i.e.AISI1016, AISI1045 and AISI304) with different thicknesses and joint configurations using a 1.5 kW CW C02 Rofin laser as a welding source and two focusing lenses with focal lengths of 127 and 190 mm. Many models were developed to predict the responses of interest for similar and dissimilar welding. Also, the main effects and the interaction effects of the process parameters on the responses were discussed and presented graphically for all materials and joint configurations. Moreover, by using the developed models the welding process was optimized by determining the optimal combination of the process input parameters at which the desired weld quality can be achieved for each material. Finally, the size and orientation of the solidified structures were related to the welding conditions. It was observed that when the heat input increases the weldbead geometry and the microstructures become bigger and coarser respectively.