The aim of this study was to determine the influence of four innovative extraction techniques: ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE), supercritical \(CO_{2}\) extraction (\(SC-CO_{2}\)) and subcritical water extraction (SWE) on the yield and content of bioactive compounds in tobacco waste extracts. Three fractions of tobacco waste, generated during the industrial processing of leaves (scrap, dust and midrib), were used for the extractions and were compared with the leaf as the starting material. Volatile compounds, phenolic compounds and nicotine were determined in the extracts using liquid and/or gas chromatography. Additionally, total phenol content and antioxidant activity were determined using spectrophotometric assays. In \(SC-CO_{2}\) extracts, the fatty acid composition was determined using gas chromatography with a flame ionization detector. Based on the obtained results, a significant influence of the applied process parameters on the responses (extraction yield, chlorogenic acid content and nicotine) was observed. Using the response surface methodology, the optimal parameters of each extraction technique were determined. Of the four extraction techniques observed, UAE yielded the highest chlorogenic acid content, while MAE proved to be suitable for nicotine extraction. Using SWE, extracts rich in phenolic compounds and nicotine were obtained, but due to the application of higher temperatures (200-250 °C), the formation of degradation products was observed. \(SC-CO_{2}\) showed high selectivity for the extraction of non-polar compounds, particularly targeted fatty acids (the dominant was palmitic acid) and volatile compounds (nicotine was the most abundant). Among the three wastes observed, the scrap proved to be the richest in bioactive compounds. In order to obtain completely exhaust waste material, a two-stage extraction process (\(SC-CO_{2}\) + SWE) was conducted on the scrap. With twostage extraction (\(SC-CO_{2}\) + SWE), the highest extraction efficiency (74.05%) and significantly higher abundance of nicotine (4.67%) and of phenolic compounds (chlorogenic acid (0.74%), neochlorogenic acid (0.46%) and rutin (1.03%)) were obtained. Therefore, two-stage extraction (\(SC-CO_{2}\) + SWE) represents an innovative approach to the valorization of tobacco waste.