The dysregulation of ribosome biogenesis is a hallmark of cancer, facilitating tumor progression through various mechanisms. This review explores the intricate interplay between ribosome biogenesis and cancer development, highlighting how key oncogenic signaling pathways regulate ribosome biogenesis. Recent studies reveal that ribosomes play multifaceted roles beyond protein synthesis, influencing processes such as stem cell-like properties maintenance and epithelial-mesenchymal transition (EMT). Interference with ribosome biogenesis, particularly through RNA Pol I inhibition, triggers a stress response leading to nucleolar integrity loss and G1-cell cycle arrest or cell death. These findings suggest that cancer cells may rely on heightened RNA Pol I transcription, making ribosomal RNA synthesis a potential therapeutic target. The review further discusses the potential of targeting ribosome biogenesis vulnerabilities as a promising strategy for cancer treatment.The dysregulation of ribosome biogenesis is a hallmark of cancer, facilitating tumor progression through various mechanisms. This review explores the intricate interplay between ribosome biogenesis and cancer development, highlighting how key oncogenic signaling pathways regulate ribosome biogenesis. Recent studies reveal that ribosomes play multifaceted roles beyond protein synthesis, influencing processes such as stem cell-like properties maintenance and epithelial-mesenchymal transition (EMT). Interference with ribosome biogenesis, particularly through RNA Pol I inhibition, triggers a stress response leading to nucleolar integrity loss and G1-cell cycle arrest or cell death. These findings suggest that cancer cells may rely on heightened RNA Pol I transcription, making ribosomal RNA synthesis a potential therapeutic target. The review further discusses the potential of targeting ribosome biogenesis vulnerabilities as a promising strategy for cancer treatment.