Advanced lung cancers and mesothelioma remain incurable diseases. Despite some promising new therapy strategies, predicting whether an individual patient will be sensitive to a given therapy is challenging. The purpose of this study is to establish and evaluate the efficiency of a three-dimensional spheroid model of human thoracic cancer in predicting the efficacy of drugs. Human mesothelioma and lung tumor spheroids were established from cell lines and primary cells derived from the patient. The growth kinetics and cell viability of microtumors were assessed using spheroid size and intracellular ATP level. The sensitivity of the mesothelioma spheroids to the cisplatin or cisplatin/pemetrexed combination was determined. We determined that studying the kinetics of the spheroid growth for 15 days after seeding 1000 cells/well in a 96-well plate was optimal. Monitoring the growth kinetic and intracellular ATP of spheroids allowed the identification of early changes in spheroid viability. Finally, we validated this model by measuring a dose-dependent reduction in the cell viability of mesothelioma H2052/484 spheroids treated with both first-line treatments, cisplatin and the cisplatin/pemetrexed combination. In conclusion, we have developed a three-dimensional spheroid model of thoracic tumor cells useful for tailoring the medical treatment to the specific characteristics of each patient.