<p>The global rise in bacterial infections underscores the urgent need for advanced functional materials with potent antibacterial activity. Metal-organic frameworks (MOFs), with their tunable structures and active metal centers, have emerged as promising candidates for biomedical applications. In this study, Fe-, Cu-, Zn-, and Ni-based structurally stable MOFs were synthesized using rational design strategies to achieve diverse morphologies and enhanced antibacterial performance. Electron microscopy (SEM and TEM) analyses confirmed the formation of hierarchical nanostructures with block-like and sharp-edged morphologies, validating the structural features at both micro- and nanoscale levels. The correlation between metal centers, structural features, and antibacterial activity was systematically examined, revealing that sharper morphologies significantly improve efficacy against <i>Staphylococcus aureus</i>. Notably, disc diffusion and minimum inhibitory concentration (MIC) studies demonstrated that Cu- and Zn-based MOFs with blade-like, prismatic edges exhibit superior antibacterial potency, achieving very low MIC values. These results highlight the potential of next-generation MOF-based materials to combat bacterial infections effectively at minimal concentrations, emphasizing the critical role of MIC as a benchmark for antibacterial efficacy.</p>