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Abstract Cities and companies have great potential to reduce pressures on Earth system boundaries. Science-based target setting has emerged as a powerful tool to help achieve the potential, but its uptake has been limited. Moreover, cities and companies usually develop their targets separately, even though many are co-located. Focusing on the top 200 cities and 500 companies by greenhouse gas emissions, we analyse the current state and potential of adopting science-based targets for climate. Of these key actors, 110 cities with existing net-zero targets and 22 companies with existing science-based targets could together eliminate up to 3.41 GtCO₂e of annual emissions. We argue that this reduction potential could increase by as much as 67% (to 5.70 GtCO₂e) if the cities and companies that already have targets bring their co-located counterparts on board to keep abreast of their ambitions. Using freshwater as another example, we discuss entry points for addressing interrelated Earth system boundaries through city–company collaborations. Our findings elucidate previously untapped potentials that could accelerate transformations for operating within Earth system boundaries.