The Galapagos Archipelago (Ecuador) is one of the most well-known natural sites in the world for its unique biodiversity. This sensitive ecosystem is at risk due to a problematic equilibrium between its conservation policy and development demand. To contribute to implementing integrated sustainable resource management in the Galapagos Islands, a material flow analysis (MFA) of Santa Cruz – the island with the highest anthropic pressure in the archipelago – has been performed, outlining a quantitative and qualitative assessment of the direct flow of goods throughout the system. MFA outcomes have been used to evaluate and forecast the impact of some policies and strategies on the local system, focusing in particular on fossil fuel consumption and local agricultural production. This case study stresses the need to introduce a local MFA protocol to decision-makers’ toolbox, as it provides quantitative assessments on a broad spectrum of local development issues.