Research on nearly zero-energy buildings has addressed mainly the aspects of energy saving or technical and economic optimization, while some studies have been conducted on comfort and indoor air quality. However, the potential problems that may arise in low-energy buildings during the operational phase, and especially the risk of fungal growth, which can deteriorate the indoor environment and pose a health risk to the occupants, are yet to be extensively investigated. The present work intends to analyze previous research on microbial contamination in zero-energy buildings in order to identify the possible risks that may lead to fungal formation and the possible strategies to prevent the proliferation of molds. The methodology is based on a systematic literature review and subsequent critical analysis to outline perspectives on this topic. The main results indicate that high envelope insulation and inadequate ventilation are the leading causes of fungal growth in energy-efficient buildings. The need for more detailed regulation in this area is also highlighted. The study’s outcomes underline the need for more attention to be paid to the design and management of zero-energy buildings, aiming to achieve the reduction in energy demands while ensuring the occupants’ well-being.