The reduction of the overall mass is a well-established strategy to improve the resource efficiency of vehicles. In terms of lightweight construction, the trend is to produce components consisting of dissimilar materials. Consequently, joining techniques are required that best fulfill the associated requirements. Joining based on reactive nanofoils represents an innovative approach to produce components in a multi-material design. However, nanofoils are not yet used in the industry due to the limited knowledge concerning the effective reaction characteristics during joining. Therefore, this study addresses the characterization of the thermal reaction properties of commercially available aluminum–nickel nanofoils. An experimental setup based on high-speed two-color infrared pyrometry was developed to ascertain the reaction temperature profile during the reaction time of ignited nanofoils. The layer composition of the samples and the ignition strategy were varied within the study. As a result, the effective reaction temperature profile and the duration of the reaction were determined in-situ with high temporal and spatial resolution for the first time. Furthermore, an analytic model was developed to accurately predict the reaction period with respect to the layer structures of the nanofoils. Finally, the sequence of developed intermediate aluminum-nickel phases during the reaction process was ascertained.