The widespread availability of mobile devices equipped with sensors on board is strongly pushing towards the development of smart spaces—offices, streets, hospital, airports, homes and shops equipped with sensing systems to help people find relevant information quickly and use services comfortably, often in a collaborative way. A common aspect in these scenarios is that the technology complexity is amplified by the organisational and procedural complexity of the application domain: this is in fact typical of socio-technical systems—kinds of systems that inherently need to be conceived, designed and developed taking into account both the technological and the human/organisational aspects from the earliest stages. In this paper, we select and discuss some challenges in the definition and development of adaptive socio-technical systems for smart spaces; the selected challenges aim at focusing in particular on (i) a socio-technical model and process, (ii) a multi-level integration framework, and (iii) methods and system analysis techniques for runtime adaptation. In fact, designing such systems requires the suitable combination of enabling technologies into an operational framework, integrating and coordinating a multiplicity of processes managed by complex organisations, each made up of independent and autonomous units.