SOIL ACTINOMYCETES were isolated from 10 different sites …….. in the World Heritage Site (WHS) of St. Katherine: Wadi El Deer, City center, Wadi El Talaa, Wadi El sheikh, Wadi El Arbean, Wadi El sheikh Awad, Wadi El Rutg, Om Kaisoum, Wadi Gebal, Gabal El Monagah. Simplified methods for isolation and characterization of actinomycetes recovered are described. Successful recovery was achieved on the media (S.C, 1/10 S.C and MGA). A total of 359 isolates were obtained and identified according to the standard macroscopic, microscopic as well as chemotaxonomy methods. A high percentage was obtained for Streptomyces, Nocardoides, Kitasatosporia spp. and unidentified spp., representing 30.4, 23.7, 11.4 and 29.3 %, respectively. The metabolic extracts from 250 randomly selected isolates exhibited various antimicrobial activities towards one reference culture (E. coli NCMB 11943) and two clinical cultures (Staphylococcus aureus, Candida albicans). Variable activities were obtained with different actinomycete isolates; the highest activity was against the Gram +ve Staphylococcus aureus, followed by Candida albicans and the Gram -ve Escherichia coli.Organic extracts from 243 isolates were effective in causing more than 40% Ehrlich ascites carcinoma (EAC) cell death after 120 min. Micromonspora, Pseudonocardia and Streptomyces spp. metabolic extracts caused the highest percentage of EAC cell death that averaged 70.58, 63.3 and 61.5 %, respectively. Actinomycetes isolated from WHS Heritage Site of Saint Katherine are suggested to be a potential source of bioactive metabolites. In conclusion, desert actinomycetes represent a promising source for antimicrobial and antitumor bioactive agents. More attention should be paid to desert soils as unique habitat for actinomycetes, though further scientific evidence needs to be produced to verify the importance of these actinomycetes and their metabolites.