As a great economic Solanum with ornamental value and good adaptability, Solanum aculeatissimum is considered an excellent candidate for the phytoremediation of Cadmium-contaminated soils. However, there are no studies on the involvement of S. aculeatissimum in the response and tolerance mechanisms of cadmium (Cd) stress. In the present study, S. aculeatissimum was used for the first time for physiological and transcriptomic systematic analysis under different concentrations of Cd stress. The results showed that S. aculeatissimum was indeed well tolerant to Cd and showed Cd enrichment capabilities. Under the Cd stress treatment of 50 mg/kg (Cd6), S. aculeatissimum could still grow normally. At the 90th day of Cd stress, the amount of Cd content in different parts of the plant at the same concentration was in the order of root > stem > leaf. With the extension of the stress time up to 163 d, the trend of Cd content in each part was not consistent, and the results in the root (77.74 mg/kg), stem (30.01 mg/kg), leaf (29.44 mg/kg), immature fruit (18.36 mg/kg), and mature fruit (21.13 mg/kg) of Cd peaked at Cd4, Cd5, Cd1, Cd4, and Cd4, respectively. The enrichment and transport coefficients of all treatments were greater than 1. The treatment groups with the largest and smallest enrichment coefficients were Cd4 and CK, respectively. The treatment groups with the largest and smallest transport coefficients were CK and Cd4, respectively. Malondialdehyde (MDA), peroxidase (POD), and catalase (CAT) in the antioxidant system after Cd stress treatment were significantly increased compared to the untreated group. Under cadmium stress, by using real-time quantitative PCR, four genes (SaHMA20, SaL-AO, SaPrxs4, and SaPCs) were screened for possible correlations to Cd tolerance and absorption enrichment in S. aculeatissimum. The key DEGs are mainly responsible for the metabolic pathways of heavy metal ATPases, plastocyanin protein phytocyanins (PCs), peroxidases (Prxs), and ascorbate oxidase (AAO); these differential genes are believed to play an important role in Cd tolerance and absorption enrichment in S. aculeatissimum.