“Precision nutrition” is an emerging area of nutrition research that focuses on understanding metabolic variability within and between individuals and helps develop customized dietary plans and interventions to maintain optimal individual health. It encompasses nutritional genomic (gene-nutrient interactions), epigenetic, microbiome, and environmental factors. Obesity is a complex disease that is affected by genetic and environmental factors and thus a relevant target of precision nutrition-based approaches. Recent studies have shown significant associations between obesity phenotypes (body weight, body mass index, waist circumference, and central and regional adiposity) and genetic variants, epigenetic factors (DNA methylation and noncoding RNA), microbial species, and environment (sociodemographics and physical activity). Additionally, studies have also shown that the interactions between genetic variants, microbial metabolites, and epigenetic factors affect energy balance and adiposity. These include variants in FTO, MC4R, PPAR, APOA, and FADS genes, DNA methylation in CpG island regions, and specific miRNAs and microbial species such as Firmicutes, Bacteriodes, Clostridiales, etc. Similarly, studies have shown that microbial metabolites, folate, B-vitamins, and short-chain fatty acids interact with miRNAs to influence obesity phenotypes. With the advent of next-generation sequencing and analytical approaches, the advances in precision nutrition have the potential to lead to new paradigms, which can further lead to interventions or customized treatments specific to individuals or susceptible groups of individuals. This review highlights the recent advances in precision nutrition as applied to obesity and projects the importance of precision nutrition in obesity and weight management.