Biopharmaceutical R&D stands at a crossroads. Escalating development costs, persistent clinical attrition, heightened competitive pressures, mounting regulatory complexity, and uncertain commercial rewards have made “ doing more with less” an inherently flawed strategy for success and sustainability. This one-of-a-kind book reframes the conversation, arguing that the true objective is not simply value creation, but value maximization under risk and uncertainty. By integrating decision analysis with enterprise portfolio management, it provides leaders with the intellectual and operational foundation required to make defensible, high-stakes investment decisions across drug discovery, clinical development, regulatory approval, and commercialization. Grounded in decades of real-world experience, the book builds on CREOPM, first introduced in 2012, as a pragmatic and maturity-sensitive framework designed to embed analytical rigor, strategic clarity, and disciplined governance into the fabric of R&D organizations.