Microplastics (MPs) have recently been discovered as considerable pollutants of all environmental matrices. They can contain a blend of chemicals, some of them added during the manufacture of plastic to improve their quality (additives) and others adsorbed from the surrounding environment. In light of this, a detailed study about the identification and quantification of target organic pollutants and qualitative screening of non-target compounds present on MPs was carried out in different types of samples: environmental MPs, collected from an Italian river, and pre-production MPs, taken from the plastic industry. Polychlorobiphenyls (PCBs), organochlorine pesticides (OCPs), and polycyclic aromatic hydrocarbons (PAHs) were chosen as target compounds to be quantified by Gas Chromatography-Mass Spectrometry (GC–MS), while the non-target screening was carried out by High Resolution Gas Chromatography-Mass Spectrometry (HRGC–MS). The target analysis revealed concentrations of 16 priority Polycyclic Aromatic Hydrocarbons by Environmental Protection Agency (EPA-PAHs) in the range of 29.9–269.1 ng/g; the quantification of 31 PCBs showed values from 0.54 to 15.3 ng/g, identifying CB-138, 153, 180, 52, and 101 primarily; and the detected OCPs (p,p’-DDT and its metabolites) ranged between 14.5 and 63.7 ng/g. The non-target screening tentatively identified 246 compounds (e.g., phthalates, antioxidants, UV-stabilizers), including endocrine disruptors, toxic and reprotoxic substances, as well as chemicals subjected to risk assessment and authorisation. The large assortment of plastic chemicals associated with MPs showed their role as a presumable source of pollutants, some of which might have high bioaccumulation potential, persistence, and toxicity.