Cyanide contamination from mining and industrial activities represents a severe environmental hazard due to its acute toxicity and persistence in aquatic ecosystems. Effective removal technologies are urgently required to safeguard water resources and ecological health. This study addresses this challenge by evaluating the scale-up of a TiO₂-based rotary concentrator photoreactor (RCPR) specifically engineered for the photocatalytic degradation of cyanide in contaminated water. Building on a previously developed pilot-scale reactor, the system was assessed through integrated modeling and simulation approaches to enhance design efficiency. The methodology combined geometric sizing, a one-dimensional thermal energy balance, and optical simulations conducted in SolTRACE 3.0, under site-specific environmental conditions from the Colombian Caribbean. Results demonstrated that geometric configuration, optical concentration, and material selection exerted a strong influence on reactor performance. Cyanide removal efficiency was confirmed experimentally and validated by acute toxicity bioassays using Daphnia magna, which provided ecotoxicological evidence of treatment effectiveness. Degradation kinetics closely matched mathematical predictions, underscoring the robustness of the model. In addition, scenario analyses explored alternative reactor geometries and construction materials to support real-scale deployment. Environmental efficiency indicators and cost–benefit analyses further highlighted the feasibility of this technology for mining wastewater treatment. These findings deliver technical, ecological, and economic insights that advance photocatalytic processes toward sustainable and scalable water treatment solutions.