This research focused on intervening in the optimization algorithm used by the Computational Reverse-Engineering Analysis for Scattering Experiments (CREASE) tool to analyze small-angle scattering (SAS) profiles using the Rigid-Body model. CREASE uses the genetic algorithm (GA) with dynamic adaptation as its optimization algorithm. The aim is to evaluate the performance of CREASE by replacing the GA with a Harmony Search (HS)-based metaheuristic, specifically the Nobel Global Harmony Search (NGHS), in the analysis of SAS profiles of low-concentration solutions vesicles-assembled amphiphilic macromolecules. Results showed that NGHS achieved similar accuracy to GA but with higher efficiency, achieving similar quality solutions with only one-sixth, and in some cases one-tenth, the number of fitness function evaluations used by GA. Besides, CREASE-NGHS achieved SAS profile analysis convergence with less than half the number of fitness function evaluations, saving computational resources and facilitating a more complete analysis. In addition, NGHS addressed some shortcomings of the GA optimization process and facilitated its use and adaptation to distinct types of samples for users with little experience in optimization.