BACKGROUND AND PURPOSE: Cutaneous leishmaniasis poses significant health and socioeconomic challenges, making vaccine development a top priority, especially in endemic regions. Cysteine proteases, KMP-11, and HASPB proteins are promising candidates for leishmaniasis vaccine development owing to their immunogenic properties and capacity to provoke robust immune responses, as evidenced by different investigations. This study aimed to design a recombinant chimeric protein (MEV-Fc) vaccine using multi-epitopes from these proteins. EXPERIMENTAL APPROACH: The antigens were subjected to immunoinformatic prediction and screening of HTL, CTL, and B-cell epitopes. The multi-epitope protein was designed with significantly high-scoring epitopes and suitable linkers. Natural adjuvants were then added to enhance immunogenicity. Vaccine potency was innovatively improved by covalently fusing human IgG1 Fc with multi-epitope protein. To investigate how the MEV-Fc vaccine interacts with Toll-like receptors, molecular docking, multi-scale normal mode analysis simulation, and computational immune simulation were employed to study humoral and cellular immune responses. FINDINGS/RESULTS: The results demonstrated the vaccine's antigenicity, stability, and nontoxicity. The structural validation confirmed the accuracy of the 3D models, indicating robust interactions with TLR2 and TLR4, with binding free energies of -1269.9 and -1128.7 (kcal/mol), respectively. Immune simulation results showed significant increases in IgM and IgG antibody levels following three vaccinations, along with enhanced activation of B cells, helper T cells, and cytotoxic T lymphocytes. CONCLUSION AND IMPLICATIONS: These findings provide novel insights for developing effective candidates for cutaneous leishmaniasis vaccines. However, laboratory experiments are necessary to evaluate its protective effects.