Background: Street vending is a critical component of India’s informal economy. This study assessed physical health, mental health, and quality of life among 422 street vendors in Chennai, Chengalpattu, and Kanchipuram. Methods: PHQ-14, DASS-21, and WHOQOL-BREF tools were used. Results: Males predominated in street vending, and 98% opposed passing the occupation to their children. Common health issues included diabetes, hypertension, hyperthyroidism, and asthma. About 51% had poor physical health, 22% depression, 23% anxiety, and 39% stress. Risk factors included age, marital status, education, residence, and occupation. Conclusion: Lack of education, unemployment, and economic hardship drive individuals into street vending, which is associated with significant physical and mental health challenges.