One key goal of heterogeneous catalysis study is to understand the correlation between the catalyst structure and its corresponding catalytic activity. In this review, we focus on recent strategies to synthesize well-defined Fischer-Tropsch synthesis (FTS) nanostructured catalysts and their catalytic performance in FTS. The development of those promising catalysts highlights the potentials of nanostructured materials to unravel the complex and dynamic reaction mechanism, particularly under the in situ reaction conditions. The crucial factors associated with the catalyst compositions and structures and their effects on the FTS activities are discussed with an emphasis on the role of theoretical modeling and experimental results.