The diagnosis of pulmonary aspergillosis is a critical step in initiating prompt treatment and improving patients’ prognosis. Currently, microbiological analysis of pulmonary aspergillosis involves fungal smear and culture, serum (1,3)-β-D-glucan (G) or galactomannan (GM) tests, and polymerase chain reaction (PCR). However, these methods have limitations. Recent studies have demonstrated that polymorphisms in pentraxin3 (PTX3), a soluble pattern recognition receptor, are associated with increased susceptibility to invasive aspergillosis. mNGS, a new microbial diagnostic method, has emerged as a promising alternative. It has high sensitivity in identifying pulmonary aspergillosis and can accurately distinguish species. Additionally, it outperforms other methods in detecting mixed infections and instructing the adjustment of antimicrobial treatments. As a result, mNGS has the potential to be adopted as the gold standard for the diagnosis of pulmonary aspergillosis.