To elucidate the relationships between lipid components and odor traits, this study comparatively characterized the distinct lipid compositions and flavor volatiles in giant salamander tails of different sexes via mass-spectrometry-based lipidomics and GC-IMS. A total of 3145 fat metabolites were detected in male and female giant salamander tails, with the largest contributors being triglycerides (TGs, 840) and phosphatidylcholines (PCs, 383). Notably, the contents of PCs and TGs were greater in female tails than in male tails, and the levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were also greater in the female group. Additionally, a total of 45 volatile components were detected, namely, 14 aldehydes, 14 alcohols, 9 ketones, 3 acids, 3 esters, 1 ether, and 1 amine. Alcohols (29.96% to 34.85%) and aldehydes (21.07% to 22.75%) were the predominant volatiles. Multivariate statistical analysis revealed 22 key differential fats and 26 differential odor substances as distinguishing labels between sexes. Correlation analysis revealed that the concentrations of triethylamine, dimethyl sulfide, ethanol-D, and 3-methyl butanal-D were significantly positively correlated with the concentrations of diglyceride (DG) (26:6e), cardiolipin (CL) (59:4), acylcarnitine (AcCa) (22:4), and triglyceride (TG) (52:10) (p < 0.01). Threefold cross-validation revealed that the prediction accuracies of these differential lipids and volatile compounds for sex recognition via the random forest model were 100%. These findings might not only provide insight into the effects of sexes on the lipid and volatile profiles of giant salamander tails but also provide clues for their gender recognition.