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Monosymptomatic nocturnal enuresis (MNE) imposes a notable clinical and psychosocial burden, yet no economic evaluations have been conducted in Thailand. This study conducted the cost-utility analysis (CUA) and budget impact analysis (BIA) of desmopressin acetate compared with imipramine and no treatment in children aged ≥ 7 years with MNE who have not responded to behavioural management and not responded, or expected not to respond, to alarm therapy. A CUA was conducted from a partial societal perspective, and a BIA was undertaken from a payer perspective. Model parameters were source from published evidence and expert opinion. Desmopressin yielded the highest quality-adjusted life years (QALYs) (9.77) and costs ($740.54). The incremental cost-effectiveness ratios were $2,385/QALY versus no treatment and $2,226/QALY versus imipramine, both below Thailand’s willingness-to-pay threshold ($4,733.73/QALY). Probabilistic sensitivity analysis indicated a 73.5–74.0% probability of cost-effectiveness. The five-year budget impact of introducing desmopressin was estimated at $26.998 million. These findings suggest that desmopressin may represent a cost-effective option for managing MNE, although its adoption would careful consideration of budgetary implications. The results provide context-specific evidence to inform policy deliberations in Thailand and may offer insights for other low- and middle-income countries.