Cities occupy 2% of the earth's surface, and yet consume 75% of the world's resources. As a major contributor to rapidly growing global energy expenditures, urban buildings are often designed and operated inefficiently despite their significant contributions to carbon emissions, triggering environmental deterioration locally and worldwide. Moreover, ongoing industrialization and urbanization pose challenges for achieving a more sustained and resilient built environment. The goal of this PhD research is to advance our understanding of urban building networks' thermal-energy dynamics in order to achieve sustainable energy conservation in the built environment. Considering buildings as networks rather than as stand-alone entities highlights the inextricably linked and interwoven relationship between urban micro-climates and buildings. With this approach, I strive to explore, mitigate, and optimize the mutual influences of the Inter-Building Effect (IBE) in dense urban settings through numerical and empirical analyses. My research also draws inspiration for investigating solutions to complex engineering problems from nature, as I seek to understand synergies between building and biological systems to discover innovative connections and integrate biology to transform buildings through sustainable building network designs. This dissertation contains three interdependent projects to explore, mitigate and optimize the IBE, respectively. I first developed a systematic approach to separately assess the complex interactions that constitute the IBE in dense urban settings and conducted cross-regional analyses in a dynamic simulation environment. Having disaggregated, quantified and understood the effects of mutual shading and mutual reflection within a network of buildings, I then, in the second project, examined different measures to mitigate the negative IBE impact under certain circumstances (e.g. directional reflective optical properties of building facades and thermal storage technologies). These two projects extended prior work that examined the potential for a biological system retroreflective surface to reduce IBE in urban building networks. Therefore, in my third project, I introduced a broad framework that draws parallels between natural and built environment systems through a levels-of-organization perspective leading to the search for an optimal status of the IBE. Inspired from a self-regulating phenomenon of plant density, I presented and discussed an approach to determine optimal urban building network density as an example for how this framework can support cross-level assessment. The findings expand and deepen our understanding of the IBE and provide insights on the strategies to mitigate the negative mutual impact within dense urban building networks. This research contributes a unique and holistic perspective on the interdependencies in the urban building network system. To design density-optimal building networks will become increasingly important to sustainable urban development and smart growth as clusters of dense urban settings continue to grow due to rapid urbanization and population migration in the next few decades.