This review delves into the strategies for early detection and characterization of Naegleria fowleri infections leading to primary amoebic meningoencephalitis (PAM). The study provides an in-depth analysis of current diagnostic approaches, including cerebrospinal fluid analysis, brain tissue examination, immunostaining techniques, and culture methods, elucidating their strengths and limitations. It explores the geographical distribution of N. fowleri, with a focus on regions near the equator, and environmental factors contributing to its prevalence. The review emphasizes the crucial role of early detection in PAM management, discussing the benefits of timely identification in treatment, personalized care, and prevention strategies. Genomic profiling techniques, such as conventional PCR, nested PCR, multiplex PCR, and real-time PCR, are thoroughly examined as essential tools for accurate and prompt diagnosis. Additionally, the study explores advanced microscopic imaging techniques to characterize N. fowleri’s morphology and behavior at different infection stages, enhancing our understanding of its life cycle and pathogenic mechanisms. In conclusion, this review underscores the potential of these strategies to improve our ability to detect, understand, and combat N. fowleri infections, ultimately leading to better patient outcomes and enhanced public health protection.