Background: Mucormycosis is a rapidly progressive and often fatal invasive fungal infection in immunocompromised patients. Diagnosis remains challenging because microscopy and culture have limited sensitivity, while targeted molecular assays may fail to detect uncommon Mucorales species. Case Presentation: We report a fatal case of disseminated Mucor indicus infection with pulmonary and cerebral involvement in a heart transplant recipient receiving immunosuppressive therapy and posaconazole prophylaxis. Initial microscopy of bronchial secretions demonstrated broad pauciseptate hyphae consistent with Mucorales, whereas targeted PCR assays remained negative. Species identification was subsequently achieved by culture, MALDI-TOF mass spectrometry, and internal transcribed spacer (ITS) sequencing. Following neurological deterioration, brain biopsy confirmed cerebral involvement histopathologically, and ITS sequencing detected M. indicus. Comparative DNA- and RNA-based metagenomic sequencing identified Mucorales sequences, although read abundance remained unexpectedly low despite extensive histopathological fungal burden. Nevertheless, independent mapping of metagenomic reads against databases comprising all genomic viral and fungal reference sequences readily identified Mucor indicus as the sole pathogen receiving significant scores. Conclusions: This case illustrates that targeted Mucorales PCR may fail to detect an uncommon species despite evidence of invasive fungal infection. Microscopy, culture, histopathology, ITS sequencing, and comprehensive metagenomic analyses provided complementary evidence for disseminated Mucor indicus infection. Integrated diagnostics combining histopathology, culture, and complementary molecular methods remain essential for accurate diagnosis of invasive mucormycosis.