The biochemical processes underlying DNA data storage, including synthesis, amplification, and sequencing, are inherently noisy. Consequently, base-level insertion, deletion, and substitution (IDS) errors, as well as sequence-level dropouts, occur and pose major challenges for reliable data retrieval. Here we introduce DNA-MGC+, a DNA storage codec designed to enable reliable and resource-efficient data retrieval under diverse operating conditions. We evaluate DNA-MGC+ across a wide range of in silico and in vitro settings, including experiments with both Illumina and Nanopore sequencing, and show that it consistently outperforms several representative codecs from the literature. In particular, DNA-MGC+ achieves simultaneous gains in sequencing depth requirements, read cost, decoding time, storage density, and error-correction capability under explicit reliability constraints. These gains persist and become more pronounced for larger files, with DNA-MGC+ remaining reliable and efficient well beyond the practical scalability limits of the benchmarked codecs. Notable performance results include reliable decoding under IDS error rates of up to 24% in synthetic scenarios, and reliable retrieval at sequencing depths below 3x with read costs below 3.5 nts/bit under electrochemical synthesis for both Illumina and Nanopore sequencing.

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