A field experiment was conducted under greenhouse conditions in the Central Laboratory for Agricultural Climate (CLAC) Dokki, Giza governorate, during the Two winter seasons of 2018/2019 and 2019/2020. The aim of the study was investigated the response of strawberry plants to the alternative substrate mixtures such as perlite with peat moss (P+P) (1:1 v/v) and perlite with vermicompost (P+V) (3:2 v/v) as well as different irrigation levels (60%, 80% and 100%) from ETo. The experimental design was split plot in three replicates. Results obtained that, strawberry cv. Festival growth responded positively by using the substrate of (P+V) as well as irrigation by 100% ETo and gave the highest values of vegetative growth characteristics. Whereas, using the substrate of (P+P) and both irrigation 80% ETo and 60% ETo were less positive than the other treatment. Nutrient content of N, P, K, Ca and Mg in leaves were increased by using (P+V) substrate and 100% irrigation level. Yield and its components (no. of fruits, fruit weight, early and total yield) as well as fruit quality parameters (TSS, acidity, Taste, vitamin C and firmness) were enhanced by using (P+V) substrate and the highest irrigation level. Water use efficiency (WUE) of strawberry enhanced by using of (P+V) substrate and irrigated with 80% follows by the treatment of 60% irrigation level. The high amount of irrigation (100%) decreased the WUE. In Egypt, we can overcome the problems of strawberry production in the traditional soils by using the alternative substrates as well as a good management for irrigation water.