Throughout human history, food has been fundamental to survival. However, unsafe food poses significant health risks, causing approximately 420,000 deaths annually, according to the World Health Organization. Those most affected are in developing and underdeveloped nations. Food safety issues often arise from food microbiome and foodborne pathogens. Microbiome, which include communities of fungi, bacteria, and viruses, interact with different food environments—raw, processed, and packaged—altering their sensory properties. This microbiome can either prevent harmful pathogens or contribute to foodborne diseases. This chapter examines food safety challenges such as managing foodborne pathogens, antimicrobial resistance, detecting microbiome, and the impacts of climate change. Other topics include food preservation, harmful microorganisms, increased contamination risks due to globalization, government regulations, food packaging, technological advancements, and the costs of control. Various scientific innovations by food scientists aim to address these challenges. The chapter concludes with a discussion of these innovations and their potential to improve food safety.