The last decade has witnessed tremendous growth in the commercial use of metal-based engineered nanomaterials (ENMs) for a wide range of products and processes. Consequently, direct and indirect release into environmental systems may no longer be considered negligible or insignificant. Yet, there is an active debate as to whether there are real risks to human or ecological health with environmental exposure to ENMs. Previous research has focused primarily on the acute effects of individual ENMs using pure cultures under controlled laboratory environments, which may not accurately reveal the ecological impacts of ENMs under real environmental conditions. The goal of this review is to assess our current understanding of ENM effects as we move from exposure of single to multiple ENMs or microbial species. For instance, are ENMs' impacts on microbial communities predicted by their intrinsic physical or chemical characteristics or their effects on single microbial populations; how do chronic ENM interactions compare to acute toxicity; does behavior under simplified laboratory conditions reflect that in environmental media; finally, is biological stress modified by interactions in ENM mixtures relative to that of individual ENM? This review summarizes key findings and our evolving understanding of the ecological effects of ENMs under complex environmental conditions on microbial systems, identifies the gaps in our current knowledge, and indicates the direction of future research.