To determine trends, mortality rates, and costs of antimicrobial resistance in invasive bacterial infections in hospitalized children, we analyzed data from Angkor Hospital for Children, Siem Reap, Cambodia, for 2007–2016. A total of 39,050 cultures yielded 1,341 target pathogens. Resistance rates were high; 82% each of Escherichia coli and Klebsiella pneumoniae isolates were multidrug resistant. Hospital-acquired isolates were more often resistant than community-acquired isolates; resistance trends over time were heterogeneous. K.