ETHER aims to provide a holistic approach for integrated terrestrial-non-terrestrial networks targeting at 100% network coverage, 99.99999% service continuity and 99.99999% reliability, with 3 times higher energy efficiency and 95% Total Cost of Ownership reduction compared to current terrestrial only deployments. To achieve these goals, ETHER develops solutions for a Unified Radio Access Network (RAN) and for the energy-efficient, AI-enabled resource management across the terrestrial, aerial and space domains, while creating the business plans driving future investments in the area. To that end, ETHER introduces and combines a series of key technologies under a unique 3D multi-layered architectural proposition that brings together: i) a UE antenna design and implementation for direct handheld access in the integrated network, ii) a robust unified waveform, iii) energy-efficient seamless horizontal and vertical handover policies, iv) a zero-touch management and network orchestrator to self-adapt to rapidly evolving traffic conditions without human intervention, v) a flexible payload system to enable programmability in the aerial and space layers, vi) joint communication, compute and storage resource allocation solutions targeting at End-to-End network performance optimization leveraging efficient and novel predictive analytics schemes, and vii) energy-efficient semantics-aware information handling techniques combined with edge computing and caching for reduced latency across the distributed 3D compute and storage continuum.