Gold-mine tailings have attracted increasing interest as alternative constituents in cement-based materials, yet their use in structural concrete remains limited by the lack of multivariable approaches capable of capturing the interaction between tailing fractions with different functional roles. In this study, a tailing-derived fine aggregate and a fine tailing sludge from the Cisneros Project (Santo Domingo, Antioquia, Colombia) were jointly incorporated into structural concrete and evaluated through a response surface methodology based on a central composite design. The tailings were characterized by physical, chemical, mineralogical, and morphological analyses, while concrete mixtures proportioned according to ACI 211 were assessed in terms of 28-day compressive strength. The statistical model revealed a significant quadratic response and a strong interaction between both incorporation variables. The most favorable strength region, based solely on 28-day compressive strength, was identified at sludge contents below 20% and tailing aggregate replacement below 90%, with the latter interpreted as a preliminary mechanical threshold rather than as a practical recommendation for field application. Higher incorporation levels led to strength losses associated with the increasing fineness of the system and greater water demand. This study demonstrates that the performance of tailing-modified structural concrete depends on the coordinated dosage of fractions with distinct roles and provides preliminary mechanical incorporation limits based solely on 28-day compressive strength. Since durability and environmental safety tests, including heavy metal/cyanide leaching, permeability, shrinkage, and chemical resistance, were not conducted, these limits should not be interpreted as definitive recommendations for long-term structural application.