The ever increasing power of computational tools encouraged by the general need for development of more sustainable technologies fuels the interest in modern optimization approaches. While simulation-based optimization has been receiving considerable attention in the past decades, it still struggles to overcome some challenges, namely excessive computation time. This study proposes a novel optimization interface, the Parallel Genetic Algorithm Interface II (PAGAN-II), which utilizes parallelization of flowsheet simulations to drastically reduce the optimization time without the need to use clustered CPUs and/or modified optimization algorithms. Results of a detailed performance study showed up to 2100% increase in computation rate when optimizing demanding process flowsheets; and approximately 300% increase when optimizing simple ones. Capabilities of the proposed interface were demonstrated by optimization of a 5 MTPA C3MR LNG technology processing 12 different feedstocks, where a 15–30% decrease in the specific energy consumption was achieved. At the same time, the algorithm increased the optimization speed 13-fold compared to the traditional approach. This translates into a reduction of optimization time from 69 days of non-stop computation to approximately 7 days.