This study provides a historical and pedagogical assessment of the Isa Bey Madrasa in Skopje, established in 1469 within the framework of the Ottoman waqf system. The research aims to examine how the madrasa contributed to the institutionalization of religion-based education in the Balkans while preserving social belonging and cultural continuity. Using an archival-historical and comparative analytical approach, the study traces the transformations of the institution from its Ottoman foundation to its present form. Although educational activities were periodically interrupted by wars, political changes, and regime transitions, the madrasa was repeatedly restructured and managed to sustain its existence. Reopened in the 1984–1985 academic year, it continues today as one of the central institutions providing formal religious education in North Macedonia. Its curriculum combines classical Islamic sciences with social sciences, natural sciences, and language courses, reflecting a synthesis of tradition and modern pedagogy. However, issues such as the language of instruction, the right to mother-tongue education, social representation, and diploma equivalency remain ongoing challenges. Overall, the study reveals that the Isa Bey Madrasa embodies both continuity and transformation in the fields of religion, culture, and education in the Balkans.