The present work proposes a methodology for optimization of a liquefied biomethane (LBM) production plant. The LBM production plant comprises amine-based absorption upgrading followed by a single expander refrigeration cycle. The processes were modeled using Aspen HYSYS® and optimized through a Sequential Quadratic Programming algorithm. Any changes in the operating conditions of the upgrading process will affect the cooling demand in the liquefaction, while the opposite is not true. Based on this, a sequential optimization approach starting with the upgrading process is proposed. In order to accommodate the connection between the processes, different objective functions were formulated for the sequential optimization approach. The results from the sequential approach were compared with an overall optimization approach, where the entire LBM plant was optimized simultaneously. The results indicate that the same solution was obtained both for the sequential approach and the simultaneous approach. For the sequential approach, however, the best result was observed when the interaction between the upgrading and liquefaction processes was accounted for by considering the effect of the upgrading process on the exergy requirement in the liquefaction process.