Complex cellular activities are believed to be coordinately regulated by genes that function in a network. Reconstructing these gene networks can provide insights into the molecular mechanisms of cell physiology and thus represents a fundamental challenge in systems biology. Elucidating the phenotype-gene interaction through the reconstruction of context-specific gene networks remains elusive. In this chapter, we present a methodology that integrates multi-level biological data to infer a cooperative gene network with respect to a specific phenotype. Our method introduces the concept of synergy and builds a network that consists of gene pairs with significant synergistic relations, which implies cooperation. We apply our method to reconstruct a synergistic gene network for saturated free fatty acid (FFA)-induced cytotoxicity, and analyze the properties of the network. Scale-free characteristics and multiple-hub genes are found in the network, revealing many important cooperative candidate genes in regulating the FFA-induced cytotoxicity. These candidates are supported by the literature.