Sandalwood (Santalum album L.) has potential to grow into various types of soil under arid as well as semi-arid regions. To find out the sustainable host plant species for sandalwood grown under stress, an RBD experiment was conducted on sandalwood grown without a host and with five selected hosts (Alternanthera sp., Azadirachata indica, Dalbergia sissoo, Melia dubia, and Aquilaria malaccensis) based on prior studies. After 6 weeks of establishment, individual and combine water and salinity stresses were applied and maintained for up to 180 days to investigate their impact on the nutrient content, concentration of osmolytes, and activities of antioxidative enzymes in sandalwood. Haustoria formation showed significant reduction under individual and combined water deficit and salinity stress. Sandalwood grown with Dalbergia sissoo and Melia dubia showed relatively higher nutrients content such as N, P, Ca, Mg, Zn, Fe, and S, which were dramatically reduced under individual and combined water deficit and salinity stress. Osmolytes concentration (proline, soluble sugars, and soluble proteins) increased with intensified stress and sandalwood accumulated higher osmolytes when grown with Dalbergia sissoo and Melia dubia. The activities of antioxidant enzymes showed a significant increase under water deficit, salinity, and combined stress compared to the control, but sandalwood grown with Dalbergia sissoo and Melia dubia exhibited higher activities. Results signify the importance of hosts i.e. Dalbergia sissoo and Melia dubia which provide suitable growth and nutrition to growing sandalwood by maintaining ion homeostasis, ROS balance, and nutrient content under water deficit, salinity, and interactive stress. Results highlighted the significance of D. sissoo and M. dubia, which may be good long-lasting host species for sandalwood production in sub-tropical climates to adapt to changing environmental conditions.