Few reports are available on children with pre-extensively drug-resistant tuberculosis (pre-XDR-TB), which is defined as Mycobacterium tuberculosis resistant to both isoniazid and rifampicin plus resistance to either a fluoroquinolone or a second-line injectable drug. Pre-XDR-TB treatment for children usually has been individualized based on drug susceptibility test (DST) results, but treatment remains challenging due to the lack of studies based on existing treatment guidelines in children and lack of availability of the new drugs. We report two cases of pre-XDR-TB in children who have responded well to individualized treatment regimens. Because toxic drugs are used for long duration, close monitoring of adverse drug reactions is important.