The pervasive presence of microplastics (MPs) in aquatic environments, coupled with their potential to act as vectors for toxic contaminants, raises significant concerns for human health. This study quantifies the health risks associated with the ingestion of microplastics and their co-contaminants in aquatic medium, considering both individual and interactive effects. The analysis encompasses four MP types (PP, PS, PET, PE) and prevalent contaminants including heavy metals (Cr, Cu, Ni, Pb), polycyclic aromatic hydrocarbons (PAHs, expressed as BaP equivalents), and plastic additives (DEHP, DBP, BPA)-to calculate individual Hazard Quotient (HQ), interaction-based Hazard Index (HIint), individual Incremental Lifetime Cancer Risk (ILCR), and interaction-based ILCR (ILCRint). The mean concentration of MPs in aqueous media was determined to be 2.19 mg/L (95 % CI), and Chronic Daily Intake (CDI) values were derived from particle counts converted to mass using polymer-specific densities. Reference Dose (RfD) values were calculated using the Weight of Evidence (WoE) approach, which integrates findings from rodent toxicity studies, identifying PP and PS as having low RfD values 25 x 10(-4) mg/kg bw/day and 8 x 10(-4) mg/kg bw/day, respectively. HQ-based toxicity rankings indicated the order of risk as PP > PS > PE > PET. Findings revealed a pronounced HIint of 18.646 x 10(3) and 16.649 x 10(6) at the 50th and 90th percentiles in children, underscoring significant synergistic effects from combined exposure to MPs and leached plastic additives. Co-contaminant scenarios further escalated health risks, with HI values reaching 52.236 in the presence of heavy metals and 53.141 with PAHs. The maximum allowable MP concentration, considering additive leaching, was estimated at 0.011 mg/L. This research highlights the need for firstly understanding the transformations of microplastic in the aquatic medium along with co-contaminants and framing regulatory measures and improved monitoring to protect human health from the growing threat of microplastic pollution. By integrating exposure modeling, dose-response assessment, and Monte Carlo simulations, the study delivers a robust framework for environmental health guidelines. It emphasizes the complex, multifaceted risks MPs pose and their associated contaminants, calling for innovative solutions to safeguard public health against this pervasive environmental challenge.