Despite possessing unique geopolitical, economic, and environmental capacities, the Makran coastal region continues to face structural challenges in its path toward innovative development. The present study aims to explain the challenges of creating an innovative ecosystem and propose strategies for its development in the Makran region by the horizon of 2045, employing a mixed-methods research approach (qualitative thematic analysis and quantitative questionnaire analysis). In the qualitative section, data were analyzed through 18 semi-structured interviews with local experts, leading to the identification of 5 main themes and 13 sub-themes. In the quantitative section, 54 questionnaires were distributed among innovation stakeholders in the region, and statistical analysis was performed using SPSS. The results indicate that Makran's innovation ecosystem is grappling with multi-level challenges, including weak technological infrastructure, institutional incoherence, brain drain, scarcity of indigenous financial support, and a weak innovation culture. Furthermore, exploratory factor analysis revealed that these challenges can be categorized into three clusters: infrastructural, institutional, and socio-cultural, accounting for 74.2% of the total variance. Nevertheless, the region's indigenous capacities in areas such as blue economy, smart logistics, renewable energies, and digital tourism have provided significant opportunities for the development of innovative clusters. Accordingly, strategies such as establishing a regional innovation coordinating council, founding a sea-oriented science and technology park, developing innovation clusters, and decentralizing innovation policies have been extracted as key pillars of the proposed indigenous model. This research offers a place-based analysis of innovation challenges and capacities in Makran, providing a strategic model for planners, policymakers, and investors, and can serve as a basis for innovative spatial policymaking in other peripheral regions of the country.