In patients with compromised immunity, invasive fungal infections represent a significant cause of mortality. Given the limited availability and drawbacks of existing first-line antifungal drugs, there is a growing interest in exploring novel targets that could facilitate the development of new antifungal agents or enhance the effectiveness of conventional ones. While previous studies have extensively summarized new antifungal targets inherent in fungi for drug development purposes, the exploration of potential targets for novel antifungal drug delivery strategies has received less attention. In this review, we provide an overview of recent advancements in new antifungal drug delivery strategies that leverage novel targets, including those located in the physio-pathological barrier at the site of infection, the infection microenvironment, fungal-host interactions, and the fungal pathogen itself. The objective is to enhance therapeutic efficacy and mitigate toxic effects in fungal infections, particularly in challenging cases such as refractory, recurrent, and drug-resistant invasive fungal infections. We also discuss the current challenges and future prospects associated with target-driven antifungal drug delivery strategies, offering important insights into the clinical implementation of these innovative approaches.
