The use of growth medium is often recommended milkweed seedlings to grow and develop after emergence, and it is affected by growth medium and local habitat conditions. The effects of growth medium and partial shade on early growth of milkweed under drought stress (Calotropis procera L.) were studied in a field experiment. A split-split plot experimental design with three replications was carried out in the nursery. The main treatment plot was divided into two levels of shade; (no shading and partial shading). Sub treatment plot1 included growth medium at four levels (G1 = clay [suitable for milkweed growth], G2 = clay + sand, G3 = clay + perlite, G4 = clay + perlite + sand) and sub treatment plot2 included drought (irrigation intervals) at six levels (D1 = 2 [control], D2 = 4, D3 = 6, D4 = 8, D5 = 10, and D6 = 12 days per for three month). The results showed that drought stress significantly decreased emergence percentage, shoot length, shoot dry weight (SDW1), root dry weight (RDW), seedling dry weight (SDW2) and vigor index (VI). The use of growth medium increased all seedling characteristics. The G3 (clay + perlite) growth medium showed the highest performance, especially in terms of emergence percentage and seedling dry weight. Partial shade improved shoot length, shoot dry weight, and vigor index. Our results showed that the best treatment for high-vigor milkweed seedlings under drought stress was G3 (clay + perlite) growth medium and partial shade.