A synthetic review of the application of multi-objective optimization models to the design of climate-responsive buildings and neighbourhoods is carried out. The review focused on the software utilized during both simulation and optimization stages, as well as on the objective functions and the design variables. The hereby work aims at identifying knowledge gaps and future trends in the research field of automation in the design of buildings. Around 140 scientific journal articles, published between 2014 and 2021, were selected from Scopus and Web of Science databases. A three-step selection process was applied to refine the search terms and to discard works investigating mechanical, structural, and seismic topics. Meta-analysis of the results highlighted that multi-objective optimization models are widely exploited for (i) enhancing building’s energy efficiency, (ii) improving thermal and (iii) visual comfort, minimizing (iv) life-cycle costs, and (v) emissions. Reviewed workflows demonstrated to be suitable for exploring different design alternatives for building envelope, systems layout, and occupancy patterns. Nonetheless, there are still some aspects that need to be further enhanced to fully enable their potential such as the ability to operate at multiple temporal and spatial scales and the possibility of exploring strategies based on sector coupling to improve a building’s energy efficiency.