Obesity is a highly prevalent global pandemic that is rapidly growing. Recent advancements in gene therapy have opened new possibilities and targets for treating, especially monogenic forms of obesity. This mini-view identified novel preclinical developments in obesity genetic treatment over the past five years. Novel strategies targeting single or multiple genes or enzymes were identified as potential alternatives for existing treatment approaches. Although clinical trials for genetic obesity treatment are yet to emerge, novel preclinical treatment approaches based on genetic traits hold promise for addressing the obesity pandemic.