Matrix metalloproteinases (MMPs) are a remarkable family of zinc-dependent endopeptidases, renowned for their pivotal role in breaking down extracellular matrix (ECM) components. This ability positions them as key players in both physiological and pathological processes, particularly in tumor-driven angiogenesis. This chapter explores the multifaceted roles of MMPs in tumor angiogenesis, focusing on their mechanisms of action, regulatory pathways, and potential as therapeutic targets in enzyme-based healthcare strategies. The study is grounded in a detailed review of current literature, emphasizing research on how MMPs contribute to ECM remodeling, guide endothelial cell migration, and regulate angiogenic factors within the tumor microenvironment. By drawing insights from peer-reviewed articles and clinical studies, this chapter provides a well-rounded perspective on how MMP activity drives tumor progression through angiogenic pathways. The findings highlight that MMPs support tumor angiogenesis by breaking ECM barriers, releasing dormant pro-angiogenic factors, and controlling the availability of angiogenesis inhibitors. Remarkably, some MMPs, such as MMP-9, exhibit dual roles, acting as both promoters and inhibitors of angiogenesis. This complexity underlines their importance in tumor biology. In conclusion, unraveling the intricate roles of MMPs in tumor angiogenesis offers exciting possibilities for therapeutic innovation. Targeting MMPs through selective inhibitors or regulating their expression could disrupt the angiogenic processes essential for tumor growth and metastasis. Such strategies present a promising path for developing effective cancer treatments, bridging the gap between enzyme research and modern healthcare solutions.