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Tourism is one of the fastest-growing and most visible sectors of the global economy, contributing significantly to boosting a nation’s economy. Currently, tourism-led economic growth considering sustainable approaches is becoming increasingly important in public policy. Recent urban and regional studies have begun to focus on the sustainability of tourism from social, economic, environmental, and cultural perspectives. The research aims to identify the most important issues and barriers to sustainable tourism development in Uzbekistan and proposes the most effective culturalization strategies to overcome those barriers. This paper involves the application of Global RPM (Globalization, Rationality, Professionalism, and Morality) analysis in combination with SANEL HERMES (Sightseeing, Admission paying, Night touring, Experiencing, Learning, Healing, Enjoying, Rest and Relaxing, Memento shopping, Eating and Drinking, and Staying) model based on data from a variety of sources, including literature review, participation interview, tourist survey, and expert questionnaire to identify and classify influencing factors that show existing barriers to sustainable tourism in Uzbekistan. Finally, a set of culturalization strategies is proposed, evaluated, and ranked by experts using a Quantitative Strategic Planning Matrix. The results of the survey have shown that tourism activities are currently not sustainable in a satisfactory manner. However, if the policymakers consider the relevant strategies and take this study into account, as well as its findings, then Uzbekistan can be made more attractive in terms of sustainable tourism.