Literature review shows that, to date, no local based method has been developed for evaluation of optimal wall constructions in a hot and humid climate from architects’ point of view. Hence, this study aims at developing a multi factor optimization model (MFOM) for comparative selection of opaque wall construction in a hot and humid climate based on four main evaluation criterion namely energy efficiency, thermal comfort, moisture control, and cost efficiency. In order to indicate the application of the MFOM, a case study methodology was employed in Kish Island, Iran, which is characterized by a hot and humid climate. Both qualitative and quantitative research methods were employed in the research process including literature and field survey, computer simulation, thermal, moisture and economic analysis finalized with a simple multi attribute rating technique (SMART) grading the outputs for final assessment. According to the results, it can be deducted that the application of the MFOM has the potential to save cost and energy, improve the thermal quality of the indoor environment while predicting the possible construction hazards posed by condensation in hot and humid climates.