The field of drug development faces significant challenges in assessing cellular-level target and off-target engagement and the mechanism of action of drugs. To address these challenges, innovative approaches like Thermal Proteome Profiling and Proteome Integral Solubility Alteration have emerged. These high-throughput techniques leverage mass spectrometry to characterize drug-protein interactions on a large scale, holding the potential to revolutionize drug discovery. However, these methods still lack a unified platform for comprehensive data analysis and comparison across different studies, hindering the ability to cross-validate findings and fully understand the implications of drug interactions. Here, we introduce DORSSAA, an integrative resource specifically designed for the comparative analysis of stability and solubility alteration assay datasets. DORSSAA hosts an extensive database containing an impressive 258,238 drug-protein interactions, including data from 18 distinct cell lines and organisms, 33 unique compounds, and a vast collection of 32,934 proteins. With the incorporation of multiple analysis tools, DORSSAA provides a user-friendly web application to support the comprehensive study of drug-target interactions. In a comprehensive case study, DORSSAA's utility is demonstrated by identifying and exploring protein-drug interactions, such as the prominent DHFR-Methotrexate interaction, across diverse cell lines and experimental conditions. This case study highlights the significance and cross-verification of drug targets using DORSSAA database. This comprehensive resource accelerates drug discovery, enhances our understanding of protein target behavior, and empowers drug discovery and optimization research. DORSSAA is available at https://dorssaa.it.helsinki.fi/.