This study presents a nonmodel-based machine learning framework for estimating engineering demand parameters (EDPs) of eccentrically braced frames with soil-structure interaction effects. The objective is to estimate residual and peak story drift ratio, peak floor acceleration, and develop fragility curves using traditional regression equations and advanced machine-learning techniques. Correction coefficients are developed to improve prediction accuracy by accounting for soil-structure interaction. A comprehensive database, including incremental dynamic analysis results of 4- and 8-story frames, is developed, consisting of 109,841 data points. The database includes fixed-base models and models with various soil-structure interaction values, subjected to 44 far-field ground motions. Four scenarios are introduced considering various input variables to compare the impact of soil-structure interaction. Findings reveal the effects of soil-structure interaction features on the performance of machine learning algorithms, increasing by up to 17.61% of the coefficient of determination. Utilizing the predicted story drift ratio, two types of fragility curves indicate more precise predictions, emphasizing the impact of soil-structure interaction effects at lower damage levels. A graphical user interface has been developed to predict fragility curves based on various inputs to promote the practical use of machine learning in engineering. Two new 4-story frames are used as case studies, subjected to unseen ground motions to assess the application of trained machine learning algorithms. Prediction errors in input-output scenarios considering soilstructure interaction range from 3% to 18% for new frames. The proposed approach for predicting EDPs is further acknowledged by evaluating a real instrumented five-story steel frame office building.