The biodegradable polymers are widely used in therapeutic surgery and pharmaceutics, in which the degradation process has drawn significant attention in recent years. In this paper, we propose a mathematical model to predict the polymer degradation in tissue engineering applications. A stochastic model is introduced to characterize the hydrolysis reaction in an elemental basis and the mass transport is also performed to investigate the diffusive transport of polymer erosion. Two representative polymeric films in different configurations are studied. It is found that for biodegradable systems, mass transport plays an important role in controlling the erosion pathway, in which the matrix configuration could be one of the key factors that determine the characteristics of erosion and drug release rates. The proposed model makes a useful benefit to the design optimization of the matrix architectures for biodegradable devices.