Geothermal resources constitute a significant portion of the world's low-carbon, renewable energy potential, with about 75% classified as low-temperature. One such potential resource exists in Precambrian basement rocks underlying the Williston Basin in southern Saskatchewan, Canada, with a reservoir temperature of 120 °C. However, geochemically induced permeability alteration in these highly reactive low-temperature granitoid resources poses a significant risk to long-term heat production. To assess and potentially mitigate this risk, we conducted a geochemical and mineralogical study of both altered and unaltered samples. Our findings facilitated the parameterization of geochemical simulations of water-rock interactions to predict mineral volume changes and, by extension, draw inferences on porosity and permeability changes resulting from these interactions. The simulations indicate an increased mineral volume in both samples, yet geothermal alteration of the unaltered, and thus more reactive, rocks induced relative mineral volume changes about 30% greater than those in the altered rocks. The resulting absolute change in porosity is 0.5 vol% for the unaltered rocks and 0.35 vol% for the altered rocks. Utilizing an empirical porosity-permeability relationship, the computed change in permeability indicates that the unaltered basement rock experienced a greater change in total permeability than the altered basement rocks. Additional calculations demonstrate the sensitivity of the porosity-permeability equation to critical porosity and power exponent, forecasting various scenarios with permeability changes ranging from 1.0 × 10−13 to 1 × 10−20 m2. Consequently, we infer that altered, permeable zones of the examined Precambrian basement rocks are likely to offer favourable conditions for sustained, multi-decade heat production, and thus should be targeted over less altered zones to justify initial capital expenditures. Globally, geothermal heat extraction from these rocks remains an underexplored yet promising resource for generating reliable, low-carbon renewable energy, crucial in our efforts to decarbonize the global economy.