For over half a century the process of economic integration of the Amazon has been based on intensive use of its renewable and nonrenewable natural resources, which have brought significant basin-wide environmental alterations. Its rural development pushed the agricultural frontier very swiftly, resulting in widespread land cover change, but agriculture in the Amazon is of low productivity and unsustainable. In addition, major new hydropower generation capacity is planned over next 30 years which will have major social and environmental impacts. Of great importance is the loss of biodiversity and continued deforestation in the Amazon that could lead to high risks of irreversible change of its tropical forests. It has been established by modeling studies that the Amazon may have two ‘tipping points’ that, once one or both are transgressed, would entail irreversible large scale forest die-back and a tendency for drier seasonal forests or impoverished tropical savanna to prevail over 30% to 50% of the basin, especially in the southern and eastern portions. These boundaries are estimated at 4°C of warming in the Amazon due to climate change or total deforested area larger than 40% of the forest cover extent in the basin. Currently, the region has warmed about 1°C over the last 60 years and total deforestation is reaching 20% of the forested area. The recent significant reductions in Amazon deforestation—close to 80% reduction in the Brazilian Amazon in the last decade—is an important contribution of the Amazonian countries to climate change mitigation by sharply reducing their GHG emissions and opens the opportunity for a novel sustainable development paradigm for the future of the Amazon. The Amazon development debate has been torn between attempting to reconcile maximizing conservation versus intensification of traditional agriculture and expansion of hydropower capacity. We argue for a Third Way in which we aggressively research, develop and scale a new high tech innovation approach that sees the Amazon as a global public good of biological assets that can enable the creation of innovative high value products, services and platforms for current and for entirely new markets through combining advanced digital, biological and material technologies of the Fourth Industrial Revolution in progress.