How would I invest if I were a vice president (VP) in charge of a drug portfolio or a venture capitalist interested in biopharmaceutical industry? In this presentation, I will address a variety of questions frequently encountered in late-stage drug development via explicit optimization of the return/investment ratio. They include: 1) how to set cost-effective Go-No Go criteria for Phase II proof-of-concept (POC) trials; 2) how to re-distribute resource when there are more POC opportunities than can afford; 3) how to deal with a possible response subpopulation; 4) how to set a cost-effective futility bar in subsequent Phase III trials; 5) what is the optimal program level strategy. The same assumptions as used in an otherwise qualitative and subjective decision process, but nothing else, will be adopted in the proposed objective decision analysis.