The adoption of the 2030 Agenda for Sustainable Development by the United Nations General Assembly, encompassing 17 Sustainable Development Goals (SDGs), established a universal framework for addressing global challenges. Within the European Union (EU), the commitment to these goals has prompted the integration of the SDGs into a strategic framework for sustainable and inclusive growth. Recognizing the need for localized and detailed monitoring to capture the nuanced progress and challenges across Europe’s diverse regions, this paper proposes a comprehensive set of regional indicators specifically designed for the European context. Through a systematic review of existing SDG monitoring frameworks at different territorial levels and an extensive methodological process, the paper identifies 116 indicators that address 75 SDG targets. This tailored set is derived from a combination of national, regional, and supranational sources. The paper discusses the critical balance between standardization for comparability and customization to accommodate unique regional characteristics. The proposed indicator set is evaluated for its capacity to reflect the holistic vision of the SDGs while allowing for effective regional benchmarking. The research emphasizes the need for robust regional data infrastructure, the importance of aligning policies with broader sustainability objectives, and the dynamic nature of indicators that can adapt to societal changes such as demographic shifts. Finally, the paper highlights the significance of a pragmatic and adaptive regional approach to SDG monitoring. The proposed indicator set is a strategic tool for policymakers, stakeholders, and practitioners, guiding Europe’s regions towards a sustainable future and contributing to the global effort to achieve the SDGs by 2030.