Guided waves-based SHM systems are of interest in the aeronautic sector due to their lightweight, long interrogation distances, and low power consumption. In this study, a bottom-up framework for the estimation of the initial investment cost (COTC) and the added weight (WAW) associated with the integration of a SHM system to an aircraft is presented. The framework provides a detailed breakdown of the activities and their costs for the sensorization of a structure using a fully wired approach or the adoption of the printed diagnostic film. Additionally, the framework considers the difference between configuring the system for Manual or Remote data acquisition. Based on the case study presented on the sensorization of a regional aircraft composite fuselage, there is a trade-off between COTC and WAW for the SHM options considered. The Wired–Manual case leads to the lowest COTC with the highest WAW, while the combination of diagnostic film with a Remote system leads to the highest COTC and the lowest WAW. These estimations capture the characteristics of each system and can be integrated into cost–benefit analyses for the final selection of a particular configuration.