A general theoretical framework is developed using free-energy functional methods to understand the effects of heterogeneity in the folding of a well-designed protein. Native energetic heterogeneity arising from nonuniformity in native stabilizing interactions, as well as entropic heterogeneity intrinsic to the topology of the native structure, are both investigated as to their impact on the folding free-energy landscape and resulting folding mechanism. Given a minimally frustrated protein, both structural and energetic heterogeneity lower the thermodynamic barrier to folding. When energy functions consist of pair interactions, designing in sufficient heterogeneity can eliminate the barrier at the folding transition temperature. Sequences with different distributions of native stabilizing interactions and correspondingly different folding mechanisms may still be good folders to the same structure. This theoretical framework allows for a systematic study of the coupled effects of energetics and topology in protein folding, and provides interpretations and predictions for future experiments which may investigate these effects.