Malate is primarily obtained from fossil resources. However, growing environmental concerns are rerouting chemical manufacturing to biomanufacturing. Despite significant ‘discovery research’ efforts for sustainable malate production, a successful industrial implementation remains elusive. A novel methanol-based l-malate biomanufacturing process using the methylotrophic bacterium Bacillus methanolicus is designed and the relationship between R&D and techno-economic feasibility is assessed. Two scenarios are modeled and compared using SuperPro Designer®. First, with limited R&D success a 65 g/L titer is achievable. Then with further strain improvement and process development titer is increased to 100 g/L. Four independent design parameters; biomass formation, CO2 evolution, methanol loss and selling price are selected to analyze techno-economic metrics of interest (yield per batch, yield on methanol, unit production cost, and net present value). Sensitivity analysis reveals the dependence of techno-economic feasibility to R&D success, while uncertainty analysis quantifies how uncertainty in process development propagates into uncertainty in process performance.