A thermoelectric generation (TEG) system has the weakness of relatively low thermoelectric conversion efficiency caused by heterogeneous temperature distribution (HgTD). Dynamic reconfiguration is an effective technique to improve its overall energy efficiency under HgTD. Nevertheless, numerous combinations of electrical switches make dynamic reconfiguration a complex combinatorial optimization problem. This paper aims to design a novel adaptive coordinated seeker (ACS) based on an optimal configuration strategy for large-scale TEG systems with series–parallel connected modules under HgTDs. To properly balance global exploration and local exploitation, ACS is based on ‘divide-and-conquer’ parallel computing, which synthetically coordinates the local searching capability of tabu search (TS) and the global searching capability of a pelican optimization algorithm (POA) during iterations. In addition, an equivalent re-optimization strategy for a reconfiguration solution obtained by meta-heuristic algorithms (MhAs) is proposed to reduce redundant switching actions caused by the randomness of MhAs. Two case studies are carried out to assess the feasibility and superiority of ACS in comparison with the artificial bee colony algorithm, ant colony optimization, genetic algorithm, particle swarm optimization, simulated annealing algorithm, TS, and POA. Simulation results indicate that ACS can realize fast and stable dynamic reconfiguration of a TEG system under HgTDs. In addition, RTLAB platform-based hardware-in-the-loop experiments are carried out to further validate the hardware implementation feasibility.