Microplastics (MPs) have rapidly emerged as a global environmental and public health concern, infiltrating ecosystems ranging from the deepest oceans to the most remote terrestrial and atmospheric regions. Their small size, chemical complexity, and remarkable persistence enable them to interact intimately with biological systems, creating a multifaceted toxicological challenge. In addition to the inherent properties of polymer particles, MPs serve as carriers for a diverse array of chemical additives and environmental contaminants including plasticizers, flame retardants, pesticides, metals, and persistent organic pollutants, amplifying their potential toxicity. As a result, MPs can induce oxidative stress, inflammation, endocrine disruption, metabolic disorders, and microbiome alterations across a wide range of organisms, with growing evidence suggesting implications for human health through ingestion, inhalation, and trophic transfer. Despite the escalating body of research, critical uncertainties persist. Variability in particle characteristics, inconsistent analytical methods, and limited understanding of chronic and low-dose exposures continue to hinder accurate risk assessment. Moreover, the increasing detection of nanoplastics raises additional concerns due to their enhanced reactivity and capacity to cross biological barriers. This review synthesizes current knowledge on the toxicity of microplastics and associated chemicals, integrating findings from environmental distribution, mechanistic toxicology, ecotoxicological effects, and human health implications. Key methodological challenges are highlighted, alongside emerging tools and policy efforts aimed at mitigating risks. By providing a comprehensive and forward-looking analysis, this review underscores the urgent need for standardized monitoring, interdisciplinary research, and regulatory action to address one of the most pervasive contaminants of the modern era.