The relevance of considering environmental variability for understanding and predicting biological responses to environmental changes has resulted in a recent surge in variability-focused ecological research. However, integration of findings that emerge across studies and identification of remaining knowledge gaps in aquatic ecosystems remain critical. Here, we address these aspects by: (1) summarizing relevant terms of variability research including the components (characteristics) of variability and key interactions when considering multiple environmental factors; (2) identifying conceptual frameworks for understanding the consequences of environmental variability in single and multi-factorial scenarios; (3) highlighting challenges for bridging theoretical and experimental studies involving transitioning from simple to more complex scenarios; (4) proposing improved approaches to overcome current mismatches between theoretical predictions and experimental observations; and (5) providing a guide for designing integrated experiments across multiple scales, degrees of control, and complexity in light of their specific strengths and limitations.