Abstract Saturn's moon Enceladus is a top candidate in the search for extraterrestrial life in our solar system. Ecological thermodynamic modeling of the plume composition data collected by NASA's Cassini mission led to the hypothesis that a hydrogenotrophic methanogenic ecosystem might exist in the putative hydrothermal vents at Enceladus's seafloor. Here we extend this approach to quantify the ecosystem's expected biomass stock and production and evaluate its detectability from the collection of plume material. We find that although a hypothetical biosphere in Enceladus's ocean could be small (<10 tons of carbon), measurable amounts of cells and organics might enter the plume. However, it is critical that missions be designed to gain meaningful insights from a negative outcome (no detection). We show that in order to sample a cell from the plume with 95% confidence, >0.1 mL of material needs to be collected. This would require material from more than 100 fly-bys through the plume or using a lander. We then consider amino acid abundance as an alternative signature and find that the absolute abundance of amino acids, such as glycine, could be very informative if a detection threshold of 1 × 10 −7 mol L −1 could be achieved. Altogether, our findings set relatively high bars on sample volume and amino acid detection thresholds, but these goals seem within the reach of near-future missions.