Background: A mesenchymal hamartoma is a rare benign tumor of the chest wall seen prenatally or at birth. Typically arising from one or more ribs, this tumor will have a rapid growth between weeks 28 and 36 of gestation, followed by a plateau and a spontaneous regression, usually within the first year of life. Clinical Findings: A 37-week 2-day, 3.48-kg female infant was admitted to the neonatal intensive care unit with a prenatally diagnosed left chest mass with a large pleural effusion and respiratory failure. Primary Diagnosis: The infant was referred to our institution with multiple chest masses on the left side, resulting in the thorax's marked deformity. Imaging studies confirmed the presence of a multifocal mesenchymal hamartoma. Interventions: At laparotomy, 3 mesenchymal hamartomas were found. The lateral mass, encompassing ribs 5 and 6, resulted in an en bloc resection. The ribs cephalad and caudal were bowed and displaced but not involved in the mesenchymal hamartoma. Complete excision of the lateral mass was done, and histopathological examination confirmed the diagnosis of mesenchymal hamartoma. Outcomes: After resection of the largest mass, the left lung reinflated appropriately, and within a few weeks, the infant was discharged home without supplemental oxygen support. Practice Recommendations: Symptomatic patients with cardiorespiratory compromise are best treated with surgical resection. In asymptomatic patients, it is best to proceed with serial imaging and conservative management with watchful waiting. Due to the rarity of the condition, data on long-term follow-up and outcomes are needed.