Cutaneous leishmaniasis (CL) is a complex vector-borne disease caused by Leishmania parasites that are transmitted by the bite of several species of infected female phlebotomine sand flies. Monthly factor analysis of climatic variables indicated fundamental variables. Principal component-based regionalization was used for recognition of climatic zones using a clustering integrated method that identified five climatic zones based on factor analysis. To investigate spatial distribution of the sand fly species, the kriging method was used as an advanced geostatistical procedure in the ArcGIS modeling system that is beneficial to design measurement plans and to predict the transmission cycle in various regions of Khuzestan province, southwest of Iran. However, more than an 80% probability of P. papatasi was observed in rainy and temperate bio-climatic zones with a high potential of CL transmission. Finding P. sergenti revealed the probability of transmission and distribution patterns of a non-native vector of CL in related zones. These findings could be used as models indicating climatic zones and environmental variables connected to sand fly presence and vector distribution. Furthermore, this information is appropriate for future research efforts into the ecology of Phlebotomine sand flies and for the prevention of CL vector transmission as a public health priority.