<p>Ammonia, a toxic nitrogenous metabolic byproduct, has garnered increasing attention for its pivotal role in tumor biology. The human body has developed intricate detoxification mechanisms to regulate ammonia homeostasis and maintain acid‒base equilibrium. Through their adaptation mechanisms, cancer cells can exploit ammonia to facilitate their growth and modulate the tumor immune microenvironment. As ammonia is a toxic substance, it can have a toxic effect on tumor, thereby inhibiting tumor growth. This article critically examines the sources and destinations of ammonia within the tumor microenvironment (TME), offering an innovative synthesis of its dual roles in both promoting and inhibiting tumor progression. Additionally, it explores therapeutic strategies targeting ammonia metabolism and anticipates future research trajectories, thereby providing valuable insights and a theoretical framework for ammonia-based therapies in oncology.</p>