Background: Antibiotic resistance occurs rapidly and naturally. However, the misuse of antibiotics is accelerating the process. And therefore, exploring new antibiotics has been a great demand in order to save people's life. Actinobacteria have been the major source of antibiotics. In this study, we focused on rare types of actinobacteria which are hard to isolate from the environment by traditional methods. Fifty rare actinobacteria were isolated from Egyptian soils, and they were screened against some bacterial pathogens (Staphylococcus aureus ATCC 6538, Pseudomonas aeruginosa ATCC 10145, Klebsiella pneumonia CCM 4415, Streptococcus mutans ATCC 25175, Escherichia coli O157:H7 ATCC 51659, and Salmonella enterica ATCC 25566). Illumina whole genome sequencing was performed for potent isolates. The whole genomes of selected rare actinobacteria were investigated via bioinformatics analysis using neighbor-joining phylogenetic analysis and Antibiotics and Secondary Metabolite Analysis SHell. Results: Isolates Rc5 and Ru87 showed the highest inhibition activity against selected Gram-positive and Gramnegative pathogens. Neighbor-joining phylogenetic analysis confirmed that isolate Rc5 belonged to Micromonospora oryzae and Micromonospora harpali with 73% bootstrap value while isolate Ru87 was grouped with Streptomyces gingianensis and Streptomyces morales with 89% bootstrap value. Bioinformatics analysis using antiSMASH 3.0 predicted 33 and 19 secondary metabolite gene clusters in Micromonospora sp. Rc5 and Streptomyces sp. Ru87, respectively. Gene annotation predicted the presence of valuable biosynthetic gene clusters in both strains such as polyketides, non-ribosomal peptides, terpenes, siderophores, bacteriocin, lasso peptide, ectoine, and lantipeptide. Conclusion: We concluded that exploring cryptic and novel biosynthetic gene clusters via Illumina whole genome sequencing and bioinformatics analysis is a useful method. We confirmed that Egyptian soil is very rich in high potential biosynthetic of rare actinobacteria. Further genetic engineering manipulation of biosynthetic pathways would eventually lead to producing novel bioactive molecules.