Moisture presents a significant challenge for flexible pavements, as it can cause a range of issues, including asphalt stripping, leading to decreased durability and service life of the pavements. This, in turn, results in higher construction and maintenance costs. The primary objective of this research is to examine the moisture sensitivity of hot asphalt mixtures by incorporating medical plastic waste (MPW) as an asphalt mix modifier. The study involved blending asphalt 60/70 with varying concentrations of MPW (ranging from 2% to 8% by weight of bitumen). The asphalt mixtures were designed according to Egyptian specifications using the Marshall method. The moisture susceptibility of both the conventional and MPW-modified asphalt mixtures was assessed through indirect tensile strength (IDT) and loss of stability tests. the test results demonstrated that adding 4% MPW yielded superior performance across most parameters. incorporating MPW significantly improved the hardness of the asphalt mixture and reduced susceptibility to moisture damage. Incorporating MPW significantly improved hardness of the asphalt mixture and reduced susceptibility to moisture damage.