Background: Streptococcus pneumoniae nasopharyngeal carriage in young children is an important source of transmission and may precede pneumococcal disease. Pneumococcal conjugate vaccines can alter circulating serotypes. Continued surveillance is needed to monitor serotype replacement, vaccine serotype coverage, and antimicrobial resistance. Methods: A prospective surveillance study was conducted in outpatient pediatric practices from October 2022 to September 2026 among children aged 2-60 months in Novi Sad, Serbia. Healthy children attending preventive visits and children with acute respiratory tract infections were enrolled. Nasopharyngeal specimens were collected and cultured for S. pneumoniae. Participant-level analyses used the first eligible specimen per child, while isolate-level analyses included all recovered isolates. Serotyping and antimicrobial susceptibility testing were performed. Theoretical vaccine serotype coverage was estimated for licensed and selected investigational pneumococcal conjugate vaccines, with 23-valent polysaccharide vaccine evaluated separately. Results: Among 3,373 included children, 911 were pneumococcal carriers, giving an overall carriage prevalence of 27.0%. Carriage was higher among children with acute respiratory tract infection than among healthy children and was also associated with daycare attendance, chronic medical conditions, age, season, and surveillance year. In total, 1,312 pneumococcal isolates were recovered, of which 87.9% were typeable. The most frequent serotypes included 11A, 10A, 15A, 15B, 23A, 23B, 19A, and 6B. Theoretical serotype coverage was 8.2% for PCV10, 17.5% for PCV13, 20.0% for PCV15, and 47.3% for PCV20. More than half of typeable isolates were non-PCV20 serotypes. Resistance was most frequent to erythromycin, clindamycin, and tetracycline, while multidrug resistance was observed in 18.1% of isolates. Penicillin G non-susceptibility was uncommon. Conclusion: Pneumococcal carriage in children aged 2-60 months in Novi Sad was associated with age, clinical presentation, season, and surveillance year and involved diverse serotypes. Continued carriage surveillance, linked with invasive-disease and antibiotic-use data, would help determine whether the observed serotype and resistance patterns persist.