Abiotic factors are the major yield-limiting factors for plants. The recent increase in contamination of arable lands with heavy metals is one of the most important causes of loss in crop productivity. On the other hand, salinity is also one of the major Abiotic stresses that affect crop production worldwide. Comparative Morpho-anatomical response of Citrullus colocynthis L. of ecotype I (Desert plant) and ecotype II (agricultural plant) under different abiotic factors were examined. The experiment was planned in a completely randomized design (CRD) with three factors and three replicates. Following levels of NaCI (0mM, 50mM, 100mM, and 200mM), NiCl2 (0µM, 50µM, 100µM, 200µM) and For combined effect of NaCI (0mM, 50mM, 100mM, 150mM, 200mM) + NiCl2 (0µM, 50µM, 100µM, 150µM, 200µM) solutions were used. The data was subjected to statistical analysis using Microsoft Excel software and Minitab statistical software for analysis of variance (ANOVA) and LSD for comparison of mean values. Morphological parameters include Root length, Shoot length, Number of leaves, Leaf area and Fresh and Dry weight of plant. While microscopic study of stem, root and leaf were observed. Both morphological and anatomical results showed that Ecotype I revealed significant tolerances than Ecotype II under these contaminations. Both Ecotypes I and II are less affected and reveal the ability to survive moderately under salt and heavy metal stresses. But under combined stress Ecotype I and II showed considerable affect as compared to single salt and metal stress. However, Ecotype I gave better responses in comparison to Ecotype II under combine stress.