Achieving zero hunger, alleviating poverty, improving nutrition and wellbeing of growing population in Asia and Africa are the main challenges during the twenty-first century with increasing land degradation, decreasing per capita availability of land and water and impacts of the climate change. In spite of available game changing technologies small farm-holders in Asia are having large yield gaps mainly due to science of discovery without science of delivery. Lack of integrated approach, compartmentalization of solutions, poor delivery systems have resulted in low adoption of improved sustainable technologies. Business as usual won’t help the farmers and there is an urgent need to transform agriculture as a business in India by adopting 4 ISECs (Innovative-integrated- scalable& sustainable environment-friendly& economically remunerative consortium-collective action) approach. Learnings from the number of scaling-up initiatives benefitting >10 million famers are documented which will enable to cross the “Death Valley of impacts” and benefit the small farm-holders in Asia and Africa ensuring food, nutrition and income security through climate resilient sustainable agriculture. The chapter describes in detail the reasons for existence of “Death Valley” of impacts, how it can be crossed and what needs to be done and explained all the three principles based on the several scaling-up initiatives undertaken benefitting millions of farmers in Asia. The results of meta-analysis undertaken by the CERES 2030 team also described as confirmatory statements for the learnings from scaling-up initiatives.