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Antimicrobial resistance (AMR) poses a global and developmental threat to humanity. The rapid emergence and spread of drug-resistant pathogens resulted in the ineffective use of currently available antibiotics. Therefore, there is a need to continue searching for additional sources of antibiotics, such as actinomycetes, which can potentially harbor unique and effective secondary metabolites. Furthermore, it is interesting to consider poorly explored environments like volcanoes, which can be potential sources of drug leads for medically important natural products. This study reports the antimicrobial activity of actinomycetes isolated from volcanic soil samples collected from Mount Mayon, Albay, Philippines. A total of 13 out of 30 morphologically distinct actinomycete isolates showed antagonistic activity against test microorganisms. Isolate A1-08, the focus of the study, exhibited a wide spectrum of antimicrobial activity against Salmonella enterica, Klebsiella pneumoniae, Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Candida albicans, Aspergillus niger, and Fusarium sp. Moreover, A1-08 was found to have anti-methicillin resistant S. aureus (MIC= 2.50 mg/mL) and anticancer activity against human colorectal cancer (HCT116) cell line (IC50= 21.54 μg/mL). Whole-genome sequence-based phylogenetic analysis supported a novel species of Streptomyces closely related to S. olivaceus NRRL B-3009. A total of 48 biosynthetic gene clusters (BGCs) were identified that may be responsible for the biosynthesis of known and potentially novel secondary metabolites. This study concludes that Streptomyces sp. A1-08, a potentially novel …