Fusarium oxysporum f. sp. cubense Tropical Race 4 (Foc TR4) (Syn. Fusarium odoratissimum) is a devastating soil-borne pathogen that infects the roots of banana plants and causes Fusarium wilt disease. Colombia is one of the world’s leading banana producers; therefore, new uncontrolled outbreaks could have serious consequences. Despite this, little is known about the susceptibility of Musaceae lands in Colombia to Foc TR4. This work presents a pioneering study on the susceptibility of Colombian soils to Foc TR4. For this, a study was carried out to characterize climatic, edaphic, and density factors of Musaceae productive systems at the Colombian level, articulated with expert criteria to map and define areas with different levels of susceptibility to Foc R4T. These criteria are typically selected based on the existing scientific literature, consultation with domain experts, and consideration of established methods for assessing soil health and disease susceptibility in Musaceae plantations. By joining the analyzed susceptibility factors, differentiated areas were generated that imply a greater or lesser predisposition to the disease. Subsequently, a validation of the classification was made with Random Forest. The results indicate that at the level of climate, soil, and farm density as a fit factor, practically 50% of the cultivated territory of Musaceae are areas high and very highly susceptible to the pathogen (572,000 km2). The results showed that from the total Musaceae area, Antioquia, Bolívar, Chocó, and Santander turned out to be the departments with the highest proportion of very high susceptibility class of the production farms. The analysis of Random Forest classification performance shows that the model has a relatively low out-of-bag (OOB) error rate (0.023). The study on the susceptibility is highly novel and original, as it represents the first systematic investigation of Foc TR4 susceptibility in Colombian soils. This paper provides important insights into the susceptibility of Musaceae lands in Colombia to Foc TR4. The study highlights the need for ongoing monitoring, containment, and control measures to prevent the spread of this deadly pathogen and protect Colombia’s important banana industry.