This review summarizes how salinity and temperature, two key global factors driven by climate change in freshwater systems, interact with other stressors on organisms in controlled small-scale factorial experiments at the population, individual, or subindividual level (excluding mesocosm and field studies). Despite the growing interest, research following all these criteria remains limited with 156 publications of which 50% analyzed stressors + salinity, 46% stressors + temperature, and only 4% involved the triple combination. Research on the combined effect of temperature and salinity predominantly focused on metals, pesticides, and, to a lesser extent, emergent contaminants, such as microplastics and nanomaterials, encompassing various biological models and responses. In general, increased temperature amplifies the single effect of stressors, whereas salinity leads to a higher diversity of responses, with similar proportions of synergisms and antagonisms. Fish (Salmoniformes, Perciformes, and Cypriniformes) were the most studied organisms. Among Crustacea, only cladocerans of the genera Daphnia and Ceriodpahnia were considered. The present review highlights the need to include other species that play key roles in freshwater food webs and to increase triple combination studies to understand complex interactions and develop adaptation and mitigation strategies to preserve the environment and its services in this changing world.