Globally there is continuous rapid production of waste tires due to an increase in vehicle usage, which is becoming a serious environmental issue as its disposal and reuse affect sustainability negatively. With concrete being the most commonly available man-made construction material, there is a serious concern over the sustainability of natural resources mostly aggregate. One of the ways to address problems related to waste tire disposal and sustainability of natural material is by incorporating the waste tires in concrete production. In this paper, the effect of crumb rubber (CR) particles partially replacing the natural sand at 0 to 30% interval of 10%, modified with nanosilica (NS) added at 0%, 2% and 3% by weight of cement in roller-compacted concrete (RCC) was investigated. Moreover, response surface methodology (RSM) was employed to develop a model for predicting fresh density, Vebe time and compressive strengths. The result showed that 2%NS is effective in mitigating strength loss in concrete containing crumb rubber up to 10%. The addition of 2% NS to RCC with 10% CR improved its strength by 10.3%, 12.7% and 27.4% at 3 days, 7 days and 28 days, respectively. The RSM models developed were significant, and there is a good correlation between the observed values and the predicted variables. Finally, the 28-day compressive strength of RCC incorporated with CR and NS was predicted based on its 3-day and 7-day compressive strengths.