A supercritical fluid extraction (SC-CO2) was used to extract high-quality oil from tomato skin by-products. The effects of pressure and extraction time on oil yield was investigated in the study. Lycopene and β-carotene content as well as p-coumaric acid, ferulic acid, caffeic acid, chlorogenic acid, vanillic acid, epicatechin, naringenin, catechin, quercetin and luteolin were estimated. The highest oil yield of 79.00% was obtained after 80 min with a pressure of 550 bar. The resulting oleoresin in carotenoids with lycopene and β-carotene content respectively of 0.86 and 1.5 mg/100 g, this oleoresin was found to be the richest. Naringenin was the most abundant flavonoid identified with a maximum content in oleoresin extracted at 550 bar (84.04 mg/kg DW) followed by caffeic acid (26.60 mg/kg DW). A moderate radical scavenging potential was further observed. Overall, results highlight that pressure is a key parameter for the extraction bioactive oleoresin from tomato skin by-products.