Global climate change can drastically alter the distribution patterns of pathogenic microbial communities and disease vectors, thereby amplifying human populations’ vulnerability to the emergence or reemergence of infectious diseases. It also influences the occurrence and transmission of vector-borne diseases by changing the distribution of disease vectors and pathogens, posing new risks to previously unaffected populations. Early detection of potential pathogens and vectors in the environment plays a vital role in implementing proactive measures to reduce the spread of contagious diseases. Metagenomics, a culture-independent approach, is a powerful approach for studying microbial communities amid climate change. It directly identifies known and unknown pathogens from environmental samples, providing insights into microbial diversity and pathogenicity. It also aids early detection, surveillance, and risk assessment of infectious diseases associated with climate change by monitoring microbial community changes. Integrating metagenomics with environmental and climatic data offers a multidisciplinary approach to understanding the complex interactions between environmental factors, pathogens, and infectious diseases. Utilizing this highly valuable data facilitates the detection of locations where pathogens are harbored within an ecosystem and the anticipation of environments that exhibit greater vulnerability to new pathogens or outbreaks resulting from preexisting pathogens. As a result, this knowledge facilitates formulating strategies to prevent animal or human infections before the onset of severe infectious disease epidemics. Despite many advantages, several challenges are also associated with this approach. This chapter focuses on several aspects of metagenomic applications for detecting various infectious diseases and pathogens under changing climate contexts.