Direct Methanol Fuel Cells (DMFCs) have become a potential alternative for rechargeable batteries in portable electronic devices since they can operate at the higher power density (generated power over the volume of the system) of conventional rechargeable batteries; and have advantages such as a simpler system design (with the potential for low-volume lightweight stacking), eliminating the requirement for fuel reforming, and classification as a zero-emission power system. There are several challenges in DMFCs which need to be overcome before they can become commercially viable energy sources. These challenges are system durability and the design optimization of system components. The durability of the DMFCs has been investigated by considering the effects of operating factors on the degradation of a single-cell DMFC with serpentine flow channels. Degradation in the performance of the DMFC system was observed and modeled over time by a linear regression model considering the cumulative exposure of the operating factors to the fuel cell and the moving average concept in the degradation analysis. In addition, the influence of the flow fields design in the DMFC system with a focus on performance was investigated. Three bipolar/end plates with a single-channel serpentine configuration were fabricated with three different channel widths and experimentally tested the performance. To understand the details of the phenomenon and the fluidic behaviours, a computational fluid dynamics (CFD) model was developed, which showed that the diffusion of fuel to the diffusion layer was higher and the fuel distribution more uniform in the narrower channel. Their performance showed that the cell equipped with the narrowest channel width had an overall higher performance compared to the widest channel width. The results of this study could enhance the performance of DMFC by modeling the polarization and degradation behaviour of the tested DMFC and provide a better understanding of the degradation phenomenon. Furthermore, the design of the DMFCs can be improved and optimized by studying the geometry of bipolar/end plates and their effect on the performance of cells. This can result in DMFCs with higher overall efficiency that approaches the targets for commercial viability.