This paper applies selected methodologies for the measurement of the environmental and economic sustainability of the Peggy Guggenheim Collection (PGC) in Venice with a view to assessing the PGC’s sustainability and commitment to implementing selected SDGs. To assess environmental sustainability, a life cycle assessment (LCA) has been carried out. The museum is conceptualized as a “firm” that produces several outputs and needs several inputs. The results provide the number of annual CO2e (and other pollutants) emissions linked to the regular activity of the museum. The environmental cost (in EUR), linked to the impacts obtained from LCA, has been calculated. To assess economic sustainability, a survey and econometric methods were used to value services directly generated by the museum, and input/output methods were used to compute the direct and indirect impacts on the local economy. Nonetheless, PGC visitors (those who travel to Venice with the main objective of visiting the PGC) contribute to around 1.2%/1.4% of Venice’s GDP. The results from input–output tables show that, although the final demand generated by the PGC’s own activities amounted to about EUR 620 million in 2022, the economic benefits of the PGC beyond this final demand are significant and very positive due to carry-over effects. Specifically, the PGC leads to an increase in GDP of around EUR 1.200 million, with a multiplier of 1.9. In terms of employment, around 8200 jobs are associated with the presence of the PGC. The net public finance revenue also clearly benefits, with a net income of around EUR 150 million in 2022. Comparing both the environmental and economic impacts of the PGC, one can conclude that the annual activities performed by the museum are highly sustainable, with the economic pillar strongly offsetting the costs generated using natural resources. The creation of economic value, therefore, is generated in respect of environmental boundaries, even if some minor flaws can be highlighted. The connection between museums and sustainable development goals is highly recognized. The findings show the PGC’s commitment to achieving and implementing selected SDGs, including SDG 4, SDG 11, and SDG 16, by implementing actions and strategies that are aligned with these goals.