This review examines the effects of simulated microgravity on cancer cells and their response to anticancer drugs. In the unique environment of space, characterized by near-weightlessness, biological systems function differently compared to Earth’s normal gravitational conditions, potentially altering drug efficacy. As human space exploration advances, understanding pharmaceutical behavior in microgravity becomes essential for astronaut healthcare. We present comprehensive findings on how microgravity conditions, simulated using technologies such as the Rotary Cell Culture System and 3D clinostats, affect cancer cell behavior and drug sensitivity. The review analyzes how microgravity influences anticancer drug effectiveness, with evidence suggesting increased drug sensitivity in certain cancer types through mechanisms involving membrane property alterations, drug transport modifications, and signaling pathway changes. We discuss key experimental findings across various cancer models, including leukemia, gastric, ovarian, and colorectal cancers, while addressing methodological limitations of microgravity simulation research. This synthesis of current knowledge advances our understanding of cancer treatment in space environments and may offer novel insights for terrestrial therapeutic strategies.