A lung abscess is a necrotizing infection caused by microbiomes that lead to the loss of healthy lung tissue. The routine culture is a waste of time and yields false-negative results, and clinicians could only choose empiric therapy or use broad-spectrum antibiotics, which could significantly contribute to the problem of resistance or aggravate the condition. We report three patients with a routine-culture-negative lung abscess. The presenting symptoms included fever, cough, dyspnea, and chest pain, and a computed tomography scan revealed a lesion in the lungs. The bronchoalveolar lavage fluid and pleural fluid were tested for pathogens using metagenome next-generation sequencing (mNGS), and the results revealed Fusobacterium nucleatum and Streptococcus spp. (S. constellatus, S. intermedius) as the most represented microbial pathogens. Our data demonstrated that mNGS could be a promising alternative diagnostic tool for pathogen detection, and the pathogen lists indicate that it will be important to focus on the Streptococcus genus rather than the dominant Streptococcus spp. in terms of co-infection of pathogen determined by shotgun mNGS.