Many emerging and re-emerging infectious diseases have been observed over the last few decades around the globe due to population growth, international travel, environmental changes, and microbial adaptation and evolution, despite advances in the medical field. The spread of these diseases is related to complex interactions between pathogens and their hosts. Accordingly, this review summarises current knowledge on infection development and discusses methods used for detection and modeling. Recent studies have revealed the limitations of two-dimensional models and increasingly rely on 3D systems, including spheroids, organoids, and organ-on-a-chip systems, that offer more realistic tissue environments, allowing researchers to more effectively study host–pathogen interactions. Overall, the integration of complementary approaches and the development of 3D models are crucial for enhancing diagnosis, developing new therapeutic approaches, and strengthening control strategies of emerging outbreaks.