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A performance-driven sustainable urban design is an important step in adapting to local climates and improving outdoor comfort level. This study proposed investigating an urban layout optimization method, validated in an urban area in Shenyang City, a cold region, that comprises nine urban blocks. This study selected an urban block type and street width as optimization input indices and defined the percentage of acceptable universal thermal comfort index (UTCI) range as the objective. The genetic algorithm is applied to optimize and generate an urban block to maximize the percentage of acceptable UTCI range at urban block level and street level. When the comfort level is set as −17–20 °C, optimization can achieve 87.7% of acceptable UTCI in the urban block level and 90.3% at urban street level. To attain an urban layout with higher than 85% acceptable UTCI range, results found, in a cold region, multistory blocks are more suitable than high-rise blocks and open spaces; it would be better to place multistory blocks with high building enclosures on the north side to block cold wind. [ABSTRACT FROM AUTHOR]