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Insomnia affects up to 50% of hospitalized patients and is strongly associated with longer hospital stays and higher mortality rates, especially among vulnerable individuals. Despite its prevalence, it's often overlooked in clinical practice and research. Our systematic review analyzed and compared pharmacological interventions for insomnia in hospitalized patients. We searched five major databases for randomized controlled trials published before January 2024. A total of 29 trials (1913 patients, mean age 58.4 ± 9.66) were finally included. Different drug classes were evaluated, including benzodiazepines, Z-drugs, melatonin receptor agonists, antidepressants, antihistamines, alpha-2 adrenergic agonists, and dietary supplements. We conducted a network meta-analysis on drugs' efficacy across subjective sleep quality, sleep latency, total sleep duration, and nocturnal awakenings. Notably, only a minority of studies focused on fragile populations, such as geriatric and critically ill patients. Results are also discussed according to potential moderating factors (i.e., gender, age, admission setting). Our review provides a framework for the pharmacologic treatment of insomnia disorder in inpatients. Differences in study methodologies limit the generalizability of findings, highlighting the urgent need for standardized research to fill existing gaps. We therefore propose a concise protocol to guide the design of future studies on this clinically important topic.