Since the nasopharynx serves as an ecological niche for Streptococcus pneumoniae, Corynebacterium spp., Haemophilus influenzae, Moraxella catarrhalis, etc., colonization is influenced by antimicrobial treatments, host immune responses, viral infections, and vaccines, often leading to local and systemic infections. We aimed to investigate the patterns of nasopharyngeal colonization and antimicrobial susceptibility of bacterial isolates in Bulgarian individuals under 20 years of age presenting with acute, protracted, and chronic cough. We analyzed 1383 samples using conventional culture methods, MALDI-TOF MS, antimicrobial susceptibility testing, and genetic analyses for Bordetella pertussis and Mycoplasma spp. Among 896 isolates, H. influenzae was the most prevalent (26.23%), followed by M. catarrhalis (23.55%), S. pneumoniae (22.54%), and S. pyogenes causing 7.59% of infections. In children (0–10 years), M. catarrhalis (198 isolates) and H. influenzae (142 isolates) were the most common pathogens, followed by S. pneumoniae (73 isolates), while in those aged 10–20 years, S. pneumoniae was the most common isolate (129), followed by H. influenzae (93) and M. pneumoniae (21). Colonization in children and young adults serves as a reservoir for pathogen transmission to adults, highlighting its significant public health implications. Monitoring bacterial colonization and resistance patterns remains essential to inform targeted prevention and treatment strategies.