In the last few years, besides the concepts of embedded and interconnected systems, also the notion of Cyber-Physical Systems (CPS) has emerged: embedded computational collaborating devices, capable of sensing and controlling physical elements and, often, responding to humans. The continuous interaction between physical and computing layers makes their design and maintenance extremely complex. Uncertainty management and runtime reconfigurability, to mention the most relevant ones, are rarely tackled by available toolchains. In this context, the Cross-layer modEl-based fRamework for multi-oBjective dEsign of Reconfigurable systems in unceRtain hybRid envirOnments (CERBERO) EU project aims at developing a design environment for CPS based of two pillars: 1) a cross-layer model-based approach to describe, optimize, and analyze the system and all its different views concurrently and 2) an advanced adaptivity support based on a multi-layer autonomous engine. In this work, we describe the components and the required developments for seamless design of reusable and reconfigurable CPS and System of Systems in uncertain hybrid environments.