Ion exchange resins and immobilized lipase as heterogeneous catalysts are used to synthesize biodiesel for alternative fossil fuels. The use of ion exchange resins in the solid and activated phase can ease the separation process. Furthermore, resins can be reactivated and used repeatedly, reducing the need for catalysts. On the other hand, an immobilized enzyme is biodegradable and can catalyze the transesterification process to produce biodiesel with a lower alcohol-to-oil ratio, minimizing side reactions and impurities. Therefore, the catalysts used in this study are ion exchange resins, such as Lewatit MP-64, Amberlite IRA410Cl, and Diaion PK208LH, as well as immobilized Candida rugosa lipase. By using vegetable oil as a feedstock and methanol for the transesterification, biodiesel production was carried out in a packed bed reactor. The present study aims to investigate the optimum process parameters, including the concentration of resin and enzyme, resin activation time, resin types, flowrate, and stability of resin and enzyme on the biodiesel yield. The results showed that the optimum conditions for biodiesel production with ion exchange resin were 4 g of resin, activated for 3 h, and synthesized for 3 h; Lewatit obtained a biodiesel yield of 94.06%, Amberlite obtained 90.00%, and Diaion obtained 73.88%. Additionally, the stability test of the reactivated Lewatit resin showed that it still has the capability of producing biodiesel with a yield of more than 80% after three regeneration cycles. In contrast, Candida rugosa lipase as was immobilized by entrapment in sodium alginate before being used in the biodiesel production for 12 h. The results showed that lower flowrate in enzymatic biodiesel synthesis produced a higher amount of biodiesel, of up to 71.1%. Nonetheless, immobilized lipases can be used up to three times without a significant loss in biodiesel yield.