The aim of this study was to investigate the physicochemical characteristics and volatile flavor of fried tilapia skins under three frying methods. Conventional deep-fat frying usually increases the oil content of the fried fish skin and leads to lipid oxidation, which reduces the product quality. Alternative frying methods, such as air frying for 6 and 12 min under 180 °C (AF6, and AF12) and vacuum frying at 0.085 MPa for 8 and 24 min under 120 °C (VF8, and VF24) were compared to conventional frying for 2 and 8 min under 180 °C (CF2, and CF8) for tilapia skin. Physical properties of fried skin, such as the moisture content, water activity, L* values and breaking force decreased under all frying methods, while the lipid oxidation and a*, b* values increased with the increase in frying time. In general, VF offered higher hardness of product compared to AF which had a lower breaking force. Especially AF12 and CF8 had the lowest breaking force, which indicated higher crispness. For the oil quality inside the product, AF and VF reduced conjugated dienes formation and retarded oxidation compared to CF. The results of the flavor compositions of fish skin measured using gas chromatography mass spectrometry (GC/MS) with solid phase microextraction (SPME) showed that CF obtained higher unpleasant oily odor (nonanal, 2,4-decadienal, etc.), while AF presented greater grilling flavor (pyrazine derivatives). Because fish skin fried by AF only relied on hot air, Maillard reaction derived compounds, such as methylpyrazine, 2,5-dimethylpyrazine, and benzaldehyde were the leading flavors. This made the aroma profiles of AF very different from VF and CF. Among all the approaches, AF and VF developed lower oil content, mild fat oxidation and better flavor attributes, which proves their practical applications for frying tilapia fish skin.