A methodological framework implementing laboratory activities and life cycle assessment is presented and applied to determine which parameters should be considered to develop biobased rigid polyurethane foams for thermal insulation with improved environmental performances when compared to their fossil counterparts. The framework was applied to six partially biobased (produced from bio-based polyols obtained from azelaic acid and/or lignin) and one fossil-based formulations. A comprehensive set of impact assessment categories was investigated including uncertainty and sensitivity analysis. Results proved that physical characteristics such as thermal conductivity and density are the most important variable to be optimized to guarantee better environmental performances of biobased polyurethane rigid foams for thermal insulation. Care should be taken with reference to ozone depletion potential, marine eutrophication, and abiotic depletion potential because of the uncertainty related to their results. The methylene diphenyl diisocyanate and foam production process were identified as the major sources of impacts. Overall environmental superiority of biobased polyurethanes cannot always be claimed with respect to their fossil counterpart.