Systems thinking—encompassing theories of complexity, emergence, self-organization, autopoiesis, adaptation, and complex adaptive systems—has recently informed innovative approaches to planning and design theory. Nonetheless, it has not radically influenced the disciplines related to spatial design—concerning the physical construction and transformation of the built environment—and these disciplines often struggle to address the complexity of the contexts in which they intervene. Although it is possible to identify spatial interventions that succeed in this sense, their designers do not explicitly connect their strategies to systems theories. In this respect, these interventions remain scattered good practices, but a theoretical framework that structures a systemic approach to spatial design disciplines has not yet been fully developed. For this reason, the present paper aims to accomplish three outcomes. One, to highlight the implications of systems thinking for spatial design disciplines. Two, to start framing a systemic approach to spatial design as “systemic spatial design.” Three, to show how this approach would benefit the established disciplines related to the modification and construction of the built environment—architecture, interior, urban, and landscape design—by enhancing their potential to proactively cooperate with site-specific emergent transformations and to virtuously intervene in spontaneous cycles of urban self-regeneration and decline. In this perspective, a multi-scale atlas is presented here as a transdisciplinary tool for place-specific systemic inquiry. This makes it possible to (a) explore cross-scale relationships in which specific spatial configurations are immersed; (b) frame them as parts of complex socio-spatial-environmental systems, (c) identify leverage points; and (d) monitor unpredictable cross-scale effects.