Chemical reactions underpin biological processes, and imbalances in critical biochemical pathways within organisms can lead to the onset of severe diseases. Within this context, the emerging field of “Nanocatalytic Medicine” leverages nanomaterials as catalysts to modulate fundamental chemical reactions specific to the microenvironments of diseases. This approach is designed to facilitate the targeted synthesis and localized accumulation of therapeutic agents, thus enhancing treatment efficacy and precision while simultaneously reducing systemic side effects. The effectiveness of these nanocatalytic strategies critically hinges on a profound understanding of chemical kinetics and the intricate interplay of reactions within particular pathological microenvironments to ensure targeted and effective catalytic actions. This review methodically explores in situ catalytic reactions and their associated biomaterials, emphasizing regulatory strategies that control therapeutic responses. Furthermore, the discussion encapsulates the crucial elements‐reactants, catalysts, and reaction conditions/environments‐necessary for optimizing the thermodynamics and kinetics of these reactions, while rigorously addressing both the biochemical and biophysical dimensions of the disease microenvironments to enhance therapeutic outcomes. It seeks to clarify the mechanisms underpinning catalytic biomaterials and evaluate their potential to revolutionize treatment strategies across various pathological conditions.