Hydrogen is a sustainable energy resource that can contribute towards achieving carbon neutrality. Among various hydrogen carriers, ammonia has attracted widespread attention due to its hydrogen density and ease of storage. In this study, ammonia cracking reactors with \(\text {2Ru/Al}_2\text {O}_3\) , \(\text {0.5Ru/Al}_2\text {O}_3\) , \(\text {40Ni/Al}_2\text {O}_3\) and \(\text {2Ru/La-Al}_2\text {O}_3\) are optimally designed considering actual experimental data and non-uniform heat supply conditions. First, ammonia cracking experiments are conducted at 300–600 \(^\circ\) C under a pressure condition of 5 bar for the catalysts. The associated kinetics are then estimated using MATLAB genetic algorithm (GA). Second, the optimal catalytic reactor volume is determined along with the required heat supply to achieve the desired conversion for each catalyst using process simulation program. To simulate the overall ammonia cracking including the reverse reaction at increased temperatures, the Temkin–Pyzhev kinetic model was implemented in Aspen HYSYS using Aspen Custom Modeler (ACM). Finally, the actual non-uniform heat supply condition by flue gas from a furnace is considered, and the catalytic reactor shape is determined to achieve the required heat supply while maintaining the optimal catalytic reactor volume. For each catalyst, the final reactor design that can achieve the desired conversion under the actual heat supply condition is proposed.