G protein–coupled receptors (GPCRs) represent the largest family of cell surface receptors. They orchestrate various signaling pathways, playing a central role in regulating various physiological and pathophysiological processes. Dysregulation of GPCR signaling has been intricately linked to cancer pathogenesis, including tumor growth, angiogenesis, metastasis, and immune modulation. Biased GPCR signaling occurs when a ligand preferentially activates one signaling pathway over another, leading to distinct cellular outcomes. In cancer, biased GPCR signaling represents a complex, dynamic phenomenon, significantly influencing cancer development, progression, and treatment resistance. This chapter reviews recent advances in our understanding of GPCR biased signaling in various aspects of cancer biology and explores its therapeutic potential. Given the fragmented nature of existing evidence, we integrate available literature with findings from our own proteomics studies on GPCR and β-arrestin function to provide a preliminary framework for understanding β-arrestin–mediated signaling in cancer. While this overview may capture only a limited snapshot of the broader landscape, it provides a valuable foundation for generating new hypotheses and guiding future research and drug discovery efforts in oncology.