This study analyzes critical issues in the disaster prevention design of urban three-dimensional space: 1) the lack of practical spatial planning for disaster prevention guided by safety assessment techniques; 2) the inability of current design strategies to address issues posed by different spaces within special urban areas; 3) the absence of a comprehensive qualitative-quantitative approach for the “normal-to-emergency” transition design of municipal facilities. In response, typical disaster scenarios for urban three-dimensional space are proposed. By examining relevant domestic and international cases, a disaster prevention design framework is established, encompassing three aspects: determination of planning layout, disaster prevention spaces, and disaster prevention facilities. Based on the scenario of flood backflow in underground spaces, a full-cycle design strategy of “Avoid-Withstand-Absorb” is proposed. For fire, explosion, and earthquake scenarios in multi-level street networks, a strategy for rationalizing three-dimensional evacuation systems is presented. For emergency evacuation in ultra-high spaces, the introduction of upper-level buffer zones is suggested to enhance evacuation efficiency.