Molecular Profiling (MP) of tumors is innovative progress that led to identifying targetable alterations that could be exploited to deliver personalized cancer treatment. Lack of data from the region about the clinical utility of has prompted this study. Tumor tissues from 100 consecutive adult patients with solid tumors were genomically profiled successfully using commercially available platforms. Outcomes for patients who received an MP-guided versus MP-unguided therapy were compared. Progression-Free Survival (PFS) was the primary endpoint, while Overall Survival (OS) was the secondary endpoint. Patients’ median age was 57 years, and female patients constituted 65% of the series. Thirty-one patients were newly diagnosed, and 69 patients had the MP performed upon disease recurrence or progression. Breast, lung, and colorectal cancers were the most frequent tumors. In 90 of the tested tumors, one or more aberrations were identified. In 61 patients, the MP results suggested at least one matched agent and guided therapy in 53 patients. Of all patients who received further therapy (83 patients), the median PFS was significantly longer in patients whose MP-guided versus those whose treatment was not guided (21.8 [95% CI; 14.5 - 29.1] vs. 10.9 [95% CI; 6.2 - 15.6] months, hazard ratio [HR] = 0.34 [95% CI; 0.17 - 0.69], P = 0.002). The benefit was largely shown in patients with recurrent or progressive disease (HR = 0.32 [95% CI; 0.14 - 1.20.75]; P = 0.006). While patients who received MP-guided therapy had numerically higher OS rates, that difference was not significant. This preliminary experience demonstrated MP’s feasibility for cancer patients with a significant improvement in PFS, albeit a lack of OS benefit. Further research is warranted to address the inherent challenges for the universal adoption of MP in daily practice.