Sustainable crop production is required for the semi-arid regions. Deficiencies of zinc, manganese and iron are common in calcareous soils of arid and semiarid regions due to their reduced solubility alkaline conditions. Sulfur fertilizers can increase micronutrients availability by decreasing soil pH. It seems that improvement of crop productivity and nutritional quality in semi-arid region can be achieved through integrated nutrient management. In order to investigate the influence of nano-chelated essential metals (Zn, Mn, Fe) and sulfur application (zero and 40 Kg ha-1) an experiment was carried out in Maragheh (37°23' N; 46°16' E), northwest of Iran. Phonological development, morphological and agronomic traits significantly responded to both nano-chelated metal and sulfur fertilizers. Results revealed that application of sulfur fertilizer considerably increased morphological traits such as ground cover, stem diameter, plant height and capitulum diameter. Mean comparison between nano-chelated metal showed that the highest value for seed yield and yield components (number of the capilulum per plants, seed number per capitulum and seed weight) achieved by nano-chelated Zn. The best performance was related to combined application of sulfur and nano-chelated Zn which followed by nano-chelated Fe. Seed oil content only affected by nano-chelated metals and the highest value obtained by application of nano-chelated Zn. Overall our finding revealed that improved fertilizer management and integrated application of sulfur and essential metals is required to grow safflower successfully on calcareous soils. The efficiency nano-chelated fertilizers can be noticeably increased by balanced nutrient management in semi-arid region.