The surface of matrix‐assisted laser desorption/ionization mass spectrometry target is modified for improved signal strength and detection of analytes. The developed method includes on‐target enrichment and detection of phosphopeptides/phospholipids using graphene oxide–lanthanide metal oxides (samarium, gadolinium, dysprosium, and erbium) nanocomposites. Enriched phosphopeptides are detected using material enhanced laser desorption/ionization mass spectrometry and phospholipids by laser desorption/ionization‐mass spectrometry. Nanocomposites are prepared using graphene oxide with respective metal salts at high pH. They are characterized for nano‐morphology, chemistry, porosity, composition, crystallinity, and thermal stability. Phosphopeptides enrichment protocol is developed and optimized for tryptic β‐casein digest and that of phospholipids by phosphatidylcholine standard. Statistical analyses of phosphopeptides and phospholipids from milk show overlapping results for gadolinium, dysprosium, and erbium oxide nanocomposites. GO‐Gd2O3 has better enrichment efficiency and application as LDI material. Selectivity for GO‐Dy2O3 is 1:2500, for GO‐Sm2O3 is 1:3500, and 1:4000 for GO‐Gd2O3. GO‐Er2O3 has a sensitivity of 25 fmol, whereas the highest sensitivity is down to 0.5 fmol for GO‐Gd2O3. On‐target enrichment is batch to batch reproducible with a standard deviation of <1, reduced time of enrichment to 10 min, and ease of operation compared to solid‐phase batch extraction. The developed method enriches serum phosphopeptides characteristic of cancer‐related phosphoproteins.