Shenqi Fuzheng injection (SFI), known for its ability to replenish Qi and strengthen vital energy, is frequently combined with docetaxel, a first-line chemotherapeutic agent, for the treatment of breast cancer in clinical practice. Although the combined regimen (SFI-docetaxel) demonstrated proven efficacy against breast cancer, no reports have addressed the alterations in the active concentrations of components in or pharmacokinetic behavior of SFI-docetaxel. Thus, a ultra performance liquid chromatography (UPLC) method was used to investigate alterations in the active components of SFI-docetaxel, and liquid chromatography-tandem mass spectrometry (LCMS/MS) analysis was used to characterize the pharmacokinetic behavior of both the active components of SFI and docetaxel in rabbits. After combination treatment with docetaxel, the concentrations of lobetyolin significantly decreased, whereas the concentrations of quercetin, formononetin, and astragaloside IV significantly increased (p < 0.05). Pharmacokinetics revealed that docetaxel had the longest half-life (T1/2) of 12.159 h, followed by that of astragaloside IV (T1/2 = 10.139 h), whereas all the other active components had T1/2 values less than 9 h. All the components reached the peak concentration time (Tmax) at 0.033 h, which is consistent with intravenous administration characteristics, indicating immediate drug action without an absorption phase. This work not only elucidated changes in the concentrations of active components in SFI-docetaxel but also revealed the pharmacokinetic characteristics of both the effective components and docetaxel, thereby providing significant implications for advancing integrated Chinese-Western medicine in cancer treatment and facilitating clinical applications of traditional Chinese medicine formulae.