Layout problems are an engineering task that heavily relies on project experience. During the design of a plant, various factors need to be considered. Most previous efforts on industrial layout design have focused on the arrangement of facilities in a plant. However, the area-wide layout was not thoroughly studied and the relationship between plant layout and area-wide layout was rarely mentioned. In this work, the key plant that has the greatest impact on the industrial area is figured out first, and then the coupling relationships between the key plant and the industrial area are studied by changing the occupied area and length-width ratio of the key plant. Both of them are achieved by changing the floor number. A hybrid algorithm involving the genetic algorithm (GA) and surplus rectangle fill algorithm (SRFA) is applied. Various constraints are considered to make the layout more reasonable and practical. In the case study, a refinery with 20 plants is studied and the catalytic cracking plant is found to be the key plant. After the retrofit, the total cost of the refinery is 1,806,100 CNY/a less than that before, which illustrates the effectiveness of the method.