The objective of the current study is to propose an expert system framework based on a supervised machine learning technique (MLT) to predict the seismic performance of low- to mid-rise frame structures considering soil-structure interaction (SSI). The methodology of the framework is based on examining different MLTs to obtain the highest possible accuracy for prediction. Within the MLT, a sensitivity analysis was conducted on the main SSI parameters to select the most effective input parameters. Multiple limit state criteria were used for the seismic evaluation within the process. A new global seismic assessment ratio was introduced that considers both serviceability and strength aspects by utilizing three different engineering demand parameters (EDPs). The proposed framework is novel because it enables the designer to seismically assess the structure, while simultaneously considering different EDPs and multiple limit states. Moreover, the framework provides recommendations for building component design based on the newly introduced global seismic assessment ratio, which considers different levels of seismic hazards. The proposed framework was validated through comparison using non-linear time history (NLTH) analysis. The results show that the proposed framework provides more accurate results than conventional methods. Finally, the generalization potential of the proposed framework was tested by investigating two different types of structural irregularities, namely, stiffness and mass irregularities. The results from the framework were in good agreement with the NLTH analysis results for the selected case studies, and peak ground acceleration (PGA) was found to be the most influential input parameter in the assessment process for the case study models investigated. The proposed framework shows high generalization potential for low- to mid-rise structures.