In recent years, with the growing population of immunocompromised individuals, infections caused by rare environmental molds have become increasingly prevalent and clinically significant. Due to frequent misdiagnosis and difficult clinical management, the overall disease burden of such infections poses a major challenge in clinical practice. This article aims to fill the knowledge gap by reviewing cases of rare mold infections from January 2020 to February 2026, analyzing the susceptible populations, identification techniques, antifungal susceptibility testing, and antifungal treatment strategies. By integrating clinical case data, we found that although most rare mold infections respond well to conventional antifungal therapy, a small number of cases still result in death. This phenomenon is attributed to the rarity of pathogens, the lack of recommended antifungal agents, or unrecognized intrinsic drug resistance, which poses a serious threat to clinical management and public health. Therefore, we further summarize research on natural products against these rare molds, aiming to provide new therapeutic insights for the management of these challenging infections. The significance of this review lies in systematically synthesizing fragmented case evidence into consolidated knowledge. By deeply integrating clinical information with rare mold identification, we constructed a comprehensive strategic framework covering rapid identification, targeted treatment, and the exploration of potential therapeutic agents. This provides evidence-based guidance for the future development of standardized diagnosis and treatment protocols for such rare mold infections.