Affinity purification-mass spectrometry (AP-MS) is a powerful approach for protein-protein interaction (PPI) analysis. Here, we report the development of a micro-scale immobilized metal affinity chromatography (m-IMAC) platform for rapid and reproducible purification of protein complexes prior to mass spectrometric analysis. The method was applied for mapping PPIs of Myc protein which regulates the expression of thousands of genes and plays a central role in tumorigenesis. Systematic characterization of Myc interactome is essential for understanding how a single transcription factor orchestrates such diverse biological processes. Affinity purification was performed using m-IMAC columns fabricated by photoinitiated polymerization within pipette tips (spin-tip columns), enabling efficient enrichment of Myc interacting proteins. Analysis with Label-Free Quantification (LFQ) with Data-Independent Acquisition (DIA) proteomics identified 574 Myc interacting proteins, the majority of which have not been previously reported as the Myc interactors. Two newly identified Myc associated factors were validated by biochemical assays, and the overall dataset showed good concordance with the reported Myc interactors. Gene Ontology (GO) enrichment analysis of the Myc associated proteome revealed significant enrichment in macromolecular metabolism (particularly RNA processing), regulation of gene expression, chromatin organization and remodeling. This work provides new insights into Myc mediated transcriptional regulation in proteomic level. Importantly, owing to its straightforward, rapid operation, the m-IMAC platform provides a general and efficient analytical strategy for high-throughput interactome analysis.