Space agencies and private companies strive for a permanent human presence on the Moon and ultimately on Mars. Bioprocesses have been advocated as key enablers due to their ability to transform locally available resources into added-value materials. However, the resource-efficiency and scaling of space biosystems remain poorly understood, hindering quantitative estimates of their potential performance. We leveraged extensive cultivation experiments, where a cyanobacterium (Anabaena sp. PCC 7938) was subject to conditions attainable on Mars, to develop a model that can estimate bioprocess productivity and resource-efficiency as a function of water, light, temperature, regolith minerals and perchlorates, and atmospheric carbon and nitrogen. We show that a breakeven can be reached within a few years. We discuss research lines to improve both resource efficiency and the accuracy of the model, thereby reducing the need for costly tests in space and eventually leading to a biotechnology-supported, sustained human presence on Mars.