Background/Aims: Forkhead Box (FOX) transcription factors (TF) are evolutionarily conversed regulators of gene expression that control, among others, cell cycle, metabolic homeostasis and stress response. Several FOX family members, including FOXM1 and FOXD1, are dysregulated in cancers and act as key oncogenic drivers. However, detailed information about their interaction networks and functional domains is lacking, limiting our understanding of FOX-mediated tumorigenesis. Moreover, due to the lack of well-defined binding sites, FOX proteins have long been considered "undruggable" targets for small molecule therapies. This project aims to utilize a multi-omics approach to map the interactome and transcriptionally active domains of selected oncogenic FOX proteins, thereby exploring their contribution to cancer. We will perform TurboID-based proximity dependent biotinylation to comprehensively map the unique and shared protein interactions of multiple oncogenic FOX proteins, enabling comparative network analysis of their local protein environment. Additionally, transactivation domain sequencing (tAD-seq) will be utilized on oncogenic FOX proteins to identify the shared and unique tADs that mediate their regulatory functions. By integrating these interactome and tAD-seq datasets, we expect to identify regulatory modules and conserved domains shared by oncogenic FOX proteins. Moreover, we will develop proteolysis-targeting chimeras (PROTACs) to achieve targeted degradation of selected oncogenic FOX proteins, providing new molecular insights into their oncogenic mechanisms. Our study proposes a novel multi-omics pipeline that combines proximity proteomics with functional domain profiling. This integrative approach aims to decipher how transcription factor families collaborate to maintain oncogenic programs, providing mechanistic insights and translational potential for future cancer therapeutics.