Background: Chemotherapy is one of the treatment modalities for cancer. The side effects of treatment, at times, can affect the emotional well-being of patients and their caregivers, thereby leading to distress. This paper aims at screening and identifying levels of distress among patients undergoing chemotherapy and their caregivers. Subjects and Methods: A cross-sectional study design was used. Patients (n = 102) undergoing chemotherapy in the outpatient daycare unit and their caregivers (n = 101) were screened for distress using the National Comprehensive Cancer Network distress thermometer and the problem checklist. Data were analyzed using descriptive and inferential statistics. Results: Patients (53.4%) and their caregivers (22.2%) reported experiencing moderate-to-severe levels of distress. Patients reported significant distress in the areas of physical (P = 0.000) and emotional problems, whereas caregivers reported distress in the areas of family (P = 0.000) and emotional problems. There was no significant difference in emotional problems (P = 0.05) between the patients and their caregivers. There was a positive correlation between physical and emotional problems (r = 0.760, P = 0.000). Majority of patients (85.2%) and caregivers (80.1%) showed interest to avail psycho-oncology services. Conclusions: Distress is prevalent among patients with cancer undergoing chemotherapy and their caregivers. Clinical implications highlight the need to identify and address caregiver distress during routine distress screening for patients using specific psychosocial interventions. Future research warrants the use of administering specific assessments to identify severe psychological issues, such as depression and anxiety for patients reporting severe levels of distress on the screening tool.