Solid oxide fuel cells (SOFCs) have potential to be the cleanest and most efficient option for direct conversion to electricity and heat of a wide variety of fuels, from hydrogen to hydrocarbons, coal gas, and bio-derived fuels. However, their commercialization hinges on rational design of novel materials of exceptional functionalities at lower temperatures to dramatically reduce the cost while enhancing performance and durability. To accomplish this goal, it is imperative to gain a fundamental understanding of the mechanisms of charge and mass transport along surfaces, across interfaces, and through porous electrodes in fuel cell systems. Further, new protocols must be developed to control materials structure, composition, and morphology over multiple length scales, thus producing nano-porous materials with more accessible surfaces of much higher functionalities and with shorter diffusion distances for greatly enhanced rate capabilities. Recently, we have fabricated and tested an electrode architecture derived from nanofibers of active cathode materials with enhanced electrochemical performance, multifunctional anodes with oriented porosity, nanostructured Sm-doped ceria electrolyte membranes with high ionic conductivity, and thin-film samples of proton and oxygen ion conducting electrolytes to study nanoionics effects at heterogeneous interfaces. This presentation will highlight the critical scientific challenges facing the development of a new generation of ITFCs, the latest developments in mixed-ion conducting electrolyte materials, nano-fiber-based cathodes, and catalytically-active anodes for internal reforming of methane at relatively low temperatures, and the perspectives for future-generation fuel cells that exploit nano-scale materials of significantly improved performance.