Extremophilic microorganisms thrive in some of the harshest environments on Earth. Genetic and enzymatic differences across the gradients from “neutral” to “harsh” environments render extremophiles survivors of some of the harshest environments on earth, and metal tolerance is often found in acidophiles. Acidophilic microorganisms, including microalgae, are often found at sites heavily affected by acid mine drainage and in naturally occurring acidic environments. Essential or non-essential, all metals are harmful when present at toxic levels. Cells cope with metal toxicity through exclusion, sequestration, active transport or biotransformations, all having implications to the cellular physiology. Microalgae, like other species, use different coping strategies when subjected to metal stress, which determines their threshold of metal stress tolerance. An example of an alga with a high level of metal tolerance is the extremophilic red alga Cyanidium caldarium. In this study, we have looked at the coping mechanisms C. caldarium employs to deal with zinc stress, and have compared it to the more susceptible mesophilic green alga Chlamydomonas reinhardtii. Measurements of photosynthesis, respiration, pigment levels, oxidative stress, stress protein and FTIR as a phenomics approach show that these species with contrasting Zn tolerances also have a contrasting approach to coping with Zn-induced oxidative stress. Despite its significantly lower tolerance to Zn, Chlamydomonas reinhardtii showed a robust Photosystem II (PSII) at Zn levels over EC50, and was able to regain gross photosynthetic capacity after an acclimation period to sub-toxic Zn levels, which it also maintained when subjected to further zinc challenges. This was not seen in the much more tolerant Cyanidium caldarium, which showed an affected PSII capacity at Zn levels above EC50, and decreased its photosynthetic rates when subjected to Zn stress, even after an acclimation period. Additionally, elevated reactive oxygen species (ROS) and heat shock protein 70 (HSP70) were found in the acclimated C. reinhardtii, which regained photosynthetic capacity, pointing to ROS acting as signalling molecules. The coping strategy of Cyanidium caldarium resulted in down-regulation of photosynthetic capacity, and its ROS production depended on the Zn-dose. FTIR analysis shows that Zn acclimation and stress results in modification of cellular macromolecular composition. The biological spectra were successfully applied to predicting levels of common bioindicators of environmental stress and pollution and thus, with further development, biospectroscopy might provide a useful tool in ecotoxicological studies and monitoring. These results open up questions of the role ROS signalling might play in the different coping strategies seen in microalgae and the wider implications of metal-stress-induced alterations in the nutritional quality of microalgae.