Non-tuberculous mycobacteria (NTM) and Aspergillus pulmonary co-infection occurs in patients with underlying lung disease and is rarely reported. We conducted a systematic search of NTM and Aspergillus pulmonary co-infection in PubMed, EMBASE, and Cochrane Library to identify cases published from 1977 to May 2022. We included 507 articles comprising 1538 cases (only 817 patients with partial relevant clinical data). Of these, 54.3% of patients were men, with a mean age of 57.7 years. Chronic obstructive pulmonary disease (21.1%), previous diagnosis of tuberculosis (18%), and asthma (11.1%) were the most common chronic lung diseases, and corticosteroids were used in 36.8% of patients. The most frequent symptoms were cough (68.2%), dyspnea (59.1%), and hemoptysis (34.1%). The most common radiological findings were bronchiectasis (52.3%) and cavitation (40.8%). NTM and Aspergillus were treated simultaneously in 47.3% of cases, whereas NTM-targeted therapy only was performed in 23.4% and Aspergillus only in 1.6%. The remaining 27.7% did not receive any treatment and were considered to be colonized. The global mortality rate was 43% (159/370). There was an increased prevalence of NTM and pulmonary aspergillosis among patients with underlying chronic lung diseases, which led to severe pulmonary affection with a poor global prognosis.