Nowadays most of energy supply and chemicals are produced from fossil fuels. However, environmental concerns like global warming, depletion of non-renewable resources and pollution, force to search for more sustainable alternative feedstocks. In this framework, the valorization of renewable resources is currently one of the most promising strategies for the next future. In particular, the use of biomass is ranked first for production of chemicals. One of the most attractive compounds that can be obtained from lignocellulosic biomass is Levulinic acid (LA). The present work analyses, from a technical, economic and safety standpoint, the valorization of waste biomass (OPEFB, oil palm empty fruit bunch) to LA with different methodologies. Energy demand of the plant and the separation efficiency are evaluated carrying out process simulations by the commercial software Aspen HYSYS V10. The obtained results allowed an economic analysis of the alternatives, based on the evaluation of investment and main operating costs. The alternatives were screened on the basis of net present value (NPV) of costs. Safety performance was investigated by an inherent safety assessment method. This considered toxic dispersion and fire scenarios, calculating the damage distances associated with the potential outcomes of an accident and allowing for the evaluation of a potential hazard index for each main process equipment. The choice of the optimal layout configuration for the production of LA in early phases of design allowed to address, in a time and cost-effective way, further design activities in reducing the energy demand and ensuring potentially safer plants making the whole process more sustainable.