Chemotherapy is one of the most widely used therapeutic modalities which is highly beneficial for management of various cancers. However, its effects are not uniform / similar across all the patients, particularly among those facing underlying chronic conditions like mellitus, hypertension, diabetes and hyper glycemia. Existence of these comorbidities in patients can lead to delayed recovery, higher toxicity and poor tolerance levels. The present Observational Study takes into account 105 cancer patients'records and previously published literature, reports and investigations on effects of chemotherapy in patients with and without metabolic and cardiovascular comorbidities. The Study analyzes changes in blood pressure, glucose levels, and hematological (blood related) profiles. Moreover, effects like neuropathy nausea, microsites (inflammation of mucosa), fatigue and infection rates were analyzed group wise to track variability or changes. Results of the observational study indicates that diabetic patients experienced 30-50% increase in glucose levels following chemotherapy cycles. Significant fluctuations in systolic and diastolic activities were recorded among hypertensive patients following chemotherapy. Compounded or increased physiological stress and multi organ toxicity is reported in both diabetic and Hypertensive patients. These findings underscore the critical need for integrating comorbidity assessment into oncology treatment planning. The Study concludes that personalized chemotherapy with continuous monitoring of glucose and blood pressure levels can reduce complications and enhance efficiency of treatment for patients of these comorbidities. It further emphasizes the importance of a multi-disciplinary and holistic approach involving Oncology, Endocrinology and Cardiology for Patient's healthy management.