The most influential conservation priority-setting approaches emphasize biodiversity and threats when deciding where to focus investment. However, socio-economic and political attributes of nations influence the effectiveness of conservation actions. A combination of biological and sociological variables in the context of a ‘return on investment’ framework for establishing conservation priorities was explored. While there was some overlap between megadiversity nations and return on investment priorities, only a few countries emerged as high priorities irrespective of which factors were included in the analysis. Conversely, some countries that ranked highly as priorities for conservation when focusing solely on biological metrics, did not rank highly when governance, population pressure, economic costs and conservation needs were considered (e.g. Colombia, Ecuador, Indonesia and Venezuela). No priority-setting scheme is a priori superior to alternative approaches. However, the analyses suggest that attention to governance and return on investment may alter biocentric assessments of ideal conservation investments.