A strategic investment plan to establish renewable energy source (RES) systems plays an important role in various decision-making processes, from a stakeholder in business purposes to a policy maker for public benefits. In this study, we have developed a new optimization model to establish efficient investment strategies to design and operate a biomass to hydrogen (B2H2) system, which includes the features of RES (e.g., intermittent availability) and RES technologies (e.g., low conversion efficiency) along with various external factors on energy economy (energy price fluctuation and demand uncertainty). As a result, we identified the optimal long-term plan of investment strategy including timing, utilized amount, and capacity of facilities. In addition, we performed an economic sensitivity analysis for major parameters and evaluated a sustainability of the B2H2 system using additional metrics such as energy security and environmental protection.