Hypersensitivity responses can occur with any medicine when taken at the recommended dosage (DHR). For a study, researchers sought to assess the features of desensitized children, the safety and efficacy of rapid drug desensitization (RDD) in children, and the characteristics and management of breakthrough reactions. Between February 2010 and February 2021, children who underwent RDD due to physician-diagnosed HSRs during or up to 48 hours after the infusion of various medicines were studied. Acute infections seen in patients with chronic disorders and those who needed regular drug usage were included. RDD’s findings were documented. The study included 48 patients [8.1(IQR=3.32–13.4) years old, 60.4% male] with 58 HSRs, 62.1% moderate and 5.2% severe. The majority of the patients were undergoing treatment for leukemia (41.7%), solid tumors (29.2%), and infections (6.3%). Skin tests were performed on 41 of 58 HSRs in 35 individuals, with 20 showing positive results. A total of 269 RDDs for 18 different medications were conducted. About 90% of desensitizations were accomplished with no reaction, 3.7% with mild reactions, and 5.6% with moderate reactions. Skin test positivity was the only risk factor for breakthrough responses in multivariate analysis (OR=8.5, CI=1.72–42.15, P=.009). Investigators established the safety and efficacy of RDD in children, giving children with chronic conditions and hypersensitive reactions (HSRs) first-line therapeutic alternatives.