The aims of the study were: (1) compare sociodemographic characteristics among active tuberculosis (TB) cases and their household contacts in cold and hot spot transmission areas, and (2) quantify the influence of locality, genotype and potential determinants on the rates of latent tuberculosis infection (LTBI) among household contacts of index TB cases. Parallel case-contact studies were conducted in two geographic areas classified as “cold” and “hot” spots based on TB notification and spatial clustering between January and June 2018 in Guangxi, China, using data from field contact investigations, whole genome sequencing, tuberculin skin tests (TSTs), and chest radiographs. Beijing family strains accounted for 64.6% of Mycobacterium tuberculosis (Mtb) strains transmitted in hot spots, and 50.7% in cold spots (p-value = 0.02). The positive TST rate in hot spot areas was significantly higher than that observed in cold spot areas (p-value < 0.01). Living in hot spots (adjusted odds ratio (aOR) = 1.75, 95%, confidence interval (CI): 1.22, 2.50), Beijing family genotype (aOR = 1.83, 95% CI: 1.19, 2.81), living in the same room with an index case (aOR = 2.29, 95% CI: 1.5, 3.49), travelling time from home to a medical facility (aOR = 4.78, 95% CI: 2.96, 7.72), history of Bacillus Calmette-Guérin vaccination (aOR = 2.02, 95% CI: 1.13 3.62), and delay in diagnosis (aOR = 2.56, 95% CI: 1.13, 5.80) were significantly associated with positive TST results among household contacts of TB cases. The findings of this study confirmed the strong transmissibility of the Beijing genotype family strains and this genotype’s important role in household transmission. We found that an extended traveling time from home to the medical facility was an important socioeconomic factor for Mtb transmission in the family. It is still necessary to improve the medical facility infrastructure and management, especially in areas with a high TB prevalence.