The Laser Beam Welding (LBW) of aluminum alloys has attracted significant interest from industrial sectors, including the shipbuilding, automotive and aeronautics industries, as it expects to contribute to significant cost reduction associated with the production of high-quality welds. To comprehend the behavior of welded structures in regard to their damage tolerance, the application of fracture mechanics serves as the instrumental tool. However, the methods employed overlook the changes in the microstructure within the Heat-Affected Zone (HAZ), which leads to the degradation of the mechanical properties of the material. The purpose of this study is to simulate microhardness evolution in the HAZ of AA2198-T351 LBW. The material represents the latest generation of Al-Cu-Li alloys, which exhibit improved mechanical properties, enhanced damage tolerance behavior, lower density and better corrosion and fatigue crack growth resistance than conventional Al-Cu alloys. In this work, the microhardness profile of LBW AA2198 was measured, and subsequently, through isothermal heat treatments on samples, the microhardness values of the HAZ were replicated. The conditions of the heat treatments (T, t) were selected in line with the thermal cycles that each area of the HAZ experienced during welding. ThermoCalc and DICTRA were employed in order to identify the strengthening precipitates and their evolution (dissolution and coarsening) during the weld thermal cycle. The microstructure of the heat-treated samples was studied employing LOM and TEM, and the strengthening precipitates and their characteristics (volume fraction and size) were defined and correlated to the calculations and the experimental conditions employed during welding. The main conclusion of this study is that it is feasible to imitate the microstructure evolution within the HAZ through the implementation of isothermal heat treatments. This implies that it is possible to fabricate samples for fatigue crack growth tests, enabling the experimental examination of the damage tolerance behavior in welded structures.