Ethanol is used to produce various value-added chemicals and as automobile fuel. Acetic acid hydrogenation to ethanol is of practical significance to meet the increasing market. However, limited engineering research for reactor and crude separation process for the acetic acid hydrogenation to ethanol despite the increasingly mature catalyst system. Moreover, the traditional approach of industrial reactor design mainly relies on point data and inadequately quantifies the strong coupling between reaction rate and transfers within the reactor, which is prone to local and loose design and optimization. In this work, a coupled design approach that combines kinetics with transfers is proposed for designing and optimizing the multi-tubular fixed-bed reactor for the acetic acid hydrogenation to ethanol. To efficiently achieve the products crude separation, staged cooling/flash/absorption/desorption units featuring with N-methyl-2-pyrrolidone as an absorbent is proposed, numerically designed and optimized. Further heuristic heat integration is also investigated to conserve extra energy of the preliminary process, which features that a by-product steam generated from ethanol synthesis reactor is utilized to drive the reboiler of the desorption. It is demonstrated that the heat-integrated process presents significant economic and emission advantages compared with the preliminary process, specifically with 36.5 % and 10.9 % reductions in operating cost and total annual cost respectively, as well as 58.1 % reductions in CO₂ emissions. The cost of synthesizing ethanol with 100 ktpy production is as low as 14.25 $/t. This work could provide a feasible and promising reactor and crude separation process for acetic acid hydrogenation to ethanol, which features economic, high-efficient, energy-saving, and low-carbon.