<p>Body packer syndrome involves the deliberate internal concealment of illicit drug packets for trafficking. Packet rupture or acute drug toxicity can lead to life-threatening complications. Given the variability across reported cases, a systematic review of case-based evidence is essential. Following PRISMA guidelines, this review was registered in PROSPERO (CRD420251028368). A comprehensive search of PubMed, EMBASE, Scopus, and Google Scholar identified case reports and series involving radiologically or surgically confirmed body packers. Extracted data included demographics, drug type, imaging modality, toxicology results, complications, treatment strategy, hospital stay, and outcomes. Risk of bias was assessed using Murad’s tool. Descriptive statistics, Chi-square, and Mann–Whitney U tests were used for analysis. Seventy-six cases were included. Cocaine and heroin were the most trafficked substances. Computed tomography (CT) was the most reliable imaging modality, outperforming plain radiography and ultrasonography in packet detection. Conservative management was successful in asymptomatic individuals, while surgical intervention was needed in cases of rupture or obstruction. Mortality was associated with packet rupture, poor packaging, and delayed diagnosis. Surgical cases had significantly longer hospital stays than conservative ones (<i>p</i> = 0.0025), as did ICU-admitted patients (<i>p</i> = 0.0044). Heroin cases showed longer stays compared to cocaine (<i>p</i> = 0.0102). CT is the most sensitive diagnostic tool in body packer syndrome. Conservative treatment is appropriate in stable patients. Early diagnosis, multidisciplinary coordination, and vigilance for novel concealment trends are critical to reduce morbidity and mortality.</p>