Aromatic amino acids, including tryptophan, phenylalanine, and tyrosine, are not only fundamental protein building blocks but also metabolic precursors of neuroactive molecules such as serotonin, dopamine, and norepinephrine, thereby regulating gut-brain communication, immune homeostasis, and metabolic health. Their therapeutic potential in neuropsychiatric, neurodegenerative, and metabolic diseases is substantial, but conventional supply routes are constrained by the low efficiency and poor optical purity of chemical synthesis and plant extraction, while oral administration faces hepatic first-pass metabolism, poor blood-brain barrier penetration, and off-target toxicity. Microbial cell factories offer a green route to convert renewable carbon sources such as glucose and glycerol into high-value aromatic derivatives. This review first outlines microbial biosynthetic routes. From tryptophan, one route proceeds via tryptophan hydroxylase to 5-hydroxytryptophan, then to serotonin, and further to melatonin; another proceeds through the kynurenine pathway, branching to neuroprotective kynurenic acid and neurotoxic quinolinic acid. Phenylalanine can be converted to phenethylamine or, via phenylpyruvate and phenylacetaldehyde, to 2-phenylethanol. Tyrosine is hydroxylated to L-3,4-dihydroxyphenylalanine (L-DOPA), which is decarboxylated to dopamine and further hydroxylated to norepinephrine. These routes establish the material basis for in situ synthesis by engineered probiotics. The review then analyzes key bottlenecks and engineering breakthroughs. Rate-limiting enzymes such as tryptophan hydroxylase, tyrosine hydroxylase, dopamine β-hydroxylase, and thyroid peroxidase suffer from poor prokaryotic expression, inclusion body formation and low catalytic efficiency. Cytochrome P450 systems are limited by inefficient electron transfering from P450 reductase. To address these problems, rational design guided by molecular dynamics, directed evolution coupled with biosensors, substrate-channel engineering, and reconstruction of electron transport chains have been applied. Cofactor supply is another central constraint. BH4 is absent in common chassis and is oxidized during hydroxylation; therefore, de novo BH4 synthesis and regeneration, together with reduced nicotinamide adenine dinucleotide phosphate (NADPH), reduced flavin adenine dinucleotide (FADH2), and S-adenosylmethionine (SAM) supply and recycling, must be systematically engineered. Metabolic network reprogramming, including relief of feedback inhibition, removal of competing branches, and transporter-mediated efflux, further improves flux. Through these coordinated strategies, compounds such as 5-hydroxytryptophane (5-HTP), L-DOPA, dopamine, and phenethylamine have reached gram- to tens-of-grams-per-liter titers. However, the review emphasizes that in vitro fermentation cannot be directly extrapolated to in vivo therapy. A considerable capability gap separates high-yield fermentation from live biotherapeutic products. After oral administration, engineered probiotics confront the intestinal ecosystem, including oxygen gradients, pH fluctuations, gastric acid, bile salts, digestive enzymes, nutrient scarcity, and the absence of selective antibiotics. The review dissects four interwoven challenges: genetic stability; metabolic adaptability and environmental stress; secretion and absorption efficiency; and biosafety and clinical translation. Corresponding strategies include chromosomal integration, multi-copy integration, active stabilization circuits, encapsulation and adhesion engineering, oxygen-insensitive pathway design, efflux system mining, and biosafety locks. Importantly, these four dimensions are not isolated but mutually constrained, so live biotherapeutic product design must balance them systematically rather than optimizing a single property. Looking forward, the review proposes that artificial intelligence and machine learning will accelerate custom enzyme design; synthetic microbial consortia will modularly partition pathways to reduce metabolic burden and resolve cofactor conflicts; physical signals such as ultrasound, visible or near-infrared light, and alternating magnetic fields will enable spatiotemporally precise release; and targeted delivery to extraintestinal tissues will expand applications. Collectively, this review provides a theoretical framework and technical roadmap for moving aromatic amino acid derivatives from green biomanufacturing toward next-generation living therapeutics.