Climate variability fundamentally realigns the processes by which mining-derived contaminants are generated, transported, and transformed at major scales, from mineral surface to watershed hydrology. Synthesizing the mechanistic architecture of the climate–mining–water nexus, the review shows that non-stationary hydroclimatic forcing wherein historical precipitation return periods, temperature baselines, and streamflow statistics no longer reliably predict future conditions invalidates the steady-state conditions of traditional water quality predictions. Coupled thermal hydrological geochemical biological atmospheric interactions produce behaviors that emerge at thresholds, hysteresis, and contaminant pulses, which reductionist frameworks overlook. Predictive capacity, therefore, calls for bidirectional, not parallel, integrative approaches to monitoring and modelling for observatories that discriminate within competing conceptual models and reactive transport frameworks that integrate multi-platform data in the face of formal uncertainty quantification. Adaptive management will need to replace static designs with decision architectures robust to deep uncertainty for signpost-based triggers, flexible infrastructure, and iterative learning. Facing up to the nexus will be a transdisciplinary fusion of molecular mechanisms to watershed outcomes, which can sustain prudent stewardship of waters influenced by mining during the age of accelerating climate change.