Every day, wastewater treatment requires large amounts of electricity. Microbial Fuel Cells (MFCs) can convert wastewater treatment plants from net power consumers into energy neutral/positive systems by generating electricity from wastewaters. We investigate here the design factors that have major impacts on the performance of two miniature MFCs, and, consequently, of the resulting stack of MFCs. A versatile mathematical model is provided, which simulates the complex MFC system by integrating fluid dynamic principles with mass transport phenomena and (bio)electrochemical reactions. The model is used to support an in-depth study of the two MFCs, which differ for electrode spacing, anodic volume and fluid pattern within the anodic chamber, and to associate any difference in performance to design factors. Finally, system scale-up is demonstrated by generating stacks of the two MFCs. Thanks to the versatility of the model developed, this study becomes a guide for the effective development of future miniature MFCs.