The enzyme-catalyzed route is a promising alternative to biodiesel production in order to meet the growing energy demand by using a renewable, efficient, environmentally friendly, and biodegradable fuel. However, the high cost of enzyme-catalyzed biodiesel production, especially the biocatalyst and feedstock prices, hinders the establishment of such technique. In the present work, the commercial low-expensively lipase Eversa Transform 2.0 was immobilized in flexible polyurethane (PU) foam, low-cost support, in order to obtain an economically feasible fatty acids methyl esters (FAME) synthesis from industrial fatty waste. The factorial design revealed that the best operational conditions for the proposed FAME synthesis system were 2 wt% of water, 2.0 eqv of methanol, 300 ppm of NaOH, and 500 ppm of the enzymatic cofactor. The immobilized biocatalyst (EI-PU) showed up to 72% of residual activity, in relation to free enzyme. In addition, from temperature and pH stability studies, the EI-PU was able to provide very similar behavior to the free enzyme. For FAME conversion, values above 91% were found, and the EI-PU could be reused for four cycles of FAME synthesis suggesting an economical route to this immobilized biocatalyst for future applications. This study is expected to be very valuable as an important prerequisite for a scale-up of enzymatic-FAME synthesis.