Sustainable development in structural materials is currently getting attention all around the world. Solid waste, building and demolition waste, natural resources, and their reuse are the most obvious strategies for achieving sustainability in the construction industry. Solid waste human hair fiber (HHF) with a diameter of 70 mu m and a length of 30-40 mm is used as a fiber, having a dosage of 0%, 1%, 1.5%, 2%, 3%, 4%, and 5%, while silica fume (SF) with a dosage of 0%, 5%, 10%, 15%, 20%, 25%, and 30% is used as a cement substitute. A drop of 50 mm to 75 mm slump was witnessed for the water-cement ratio used in the M20 mix design of concrete. The concrete's mechanical properties, such as compressive, split tensile, and flexural strength, were determined after 28 days of water curing. The concept of the response surface methodology (RSM) for optimizing human hair fiber concrete (HHFC) and SF substitution was used, which was validated by the polynomial work expectation. The model is statistically significant when the fluctuation of the analysis of variance (ANOVA) is analyzed using a p-value with a significance level of 0.05. The test results showed that the use of 2% human hair as fiber and 15% SF as a cementitious additive or cement replacement considerably improved the strength of concrete. The compressive, flexural, and split tensile strengths of HHFC improved by 14%, 8%, and 7%, respectively, which shows the significance of human hair and the partial replacement of cement with SF. Moreover, SEM analysis was carried out to study the microstructure of the concrete matrix.