Long-term dependence of illicit drugs impairs the function of the hypothalamic-pituitary-adrenal (HPA) axis, which regulates the secretion of endogenous steroids, cortisol, and cortisone. Thus, the present study aimed to develop a sensitive method for simultaneous determination of the multiple illicit drugs and two steroids in hair to monitor the status of illicit drug exposure and the physiological and psychological health of drug addicts. The target analytes were extracted from hair by incubation with 1 mL methanol for 24 h at 40 °C and then determined with LC-APCI+-MS/MS. The validated method showed acceptable linearity (R2 > 0.99) in the range of 1.25–250 pg/mg for cortisol and cortisone, 2.5–125 pg/mg for heroin, 2.5–1250 pg/mg for ketamine, 2.5–5000 pg/mg for methamphetamine (MAM), 2.5–250 pg/mg for 3, 4-methylenedioxymethamphetamine (MDMA), morphine, and 6-monoacetylmorphine (6-AM). Limits of quantification were 1.6, 1.2, 1.6, 1.0, 1.4, 0.3, 2.1, and 1.2 pg/mg for cortisol, cortisone, heroin, ketamine, MAM, MDMA, morphine, and 6-AM, respectively. Method recoveries were from 90–115% for all analytes. Inter-day and intra-day coefficients of variation were within 10%. Finally, this method was successfully applied to detect the aforementioned analytes in hair among female drug addicts who self-reported to be MAM abuser, heroin abuser, ketamine abuser, and abuser of mixture drugs of MAM and heroin. MAM abusers with current MAM use showed significantly higher concentrations of cortisol, MAM, and MDMA than controls with drug withdrawal.