This paper addresses the challenge of reducing the number of nodes in Look-Up Table (LUT) networks with two significant applications. First, Field-Programmable Gate Arrays (FPGAs) can be modelled as networks of LUTs, and minimizing the node count is imperative to meet resource constraints. Second, in area-oriented design space exploration for standard-cell designs, collapsing a circuit into a LUT network, restructuring it, and later remapping to the original representation helps escape local minima. Thus, the development of algorithms for optimizing and restructuring LUT networks holds considerable promise for area-oriented optimization. Substitution (also called resubstitution) is a powerful logic minimization method that can identify non-local logic dependencies and exploit them for logic minimization. State-of-the-art substitution algorithms for LUT networks rely heavily on SAT solving, limiting the number of optimization attempts and the size of the substitution sub-networks to one node mishchenko2011scalable. Conversely, our method relies on circuit simulation to increase the number of substitution candidates and enables substitutions with more than one node. The experimental results show that the proposed method identifies optimization opportunities overlooked by other methods, improving 11 out of 23 best-known results in the EPFL synthesis competition and yielding a 3.46% area reduction compared to the state-of-the-art.