The Sustainable Development Goals (SDGs) are ambitious but in deep trouble. Benefit–cost analysis can help. This Special Issue highlights 12 of the most efficient interventions to speed up progress on the SDGs with Benefit–Cost Ratios (BCRs) above 15. The approaches cover tuberculosis, education, maternal and newborn health, agricultural R&D, malaria, e-procurement, nutrition, land tenure security, chronic diseases, trade, child immunization, and skilled migration. Spanning 2023–2030, these policy approaches are estimated to cost an annual average of $41 billion (of which $6 billion is non-financial). They will realistically deliver $2.1 trillion in annual benefits, consisting of $1.1 trillion in economic benefits and 4.2 million lives saved. The pooled benefit–cost ratio of all 12 investments is 52. By prioritizing these high-impact “best buy” interventions, decision-makers can enhance resource allocation and contribute most efficiently to the SDGs.