• Parts A and B: Patients must be \>= 12 months and =\< 21 years of age at the time of study enrollment

• Patients must have had histologic verification of malignancy at original diagnosis or relapse, except in patients with diffuse intrinsic brain stem tumors, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers, including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)

‣ Part A: Patients with relapsed or refractory solid tumors or lymphoma, including patients with CNS tumors or known CNS metastases (including untreated or progressive) are eligible

⁃ Part B: Patients with progressive or recurrent DIPG (diagnosed by biopsy or imaging characteristics) and other H3 K27-altered DMG previously treated with radiation therapy

• Part A: Patients must have either measurable or evaluable disease

• Part B: Patients must have measurable disease

• Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life

• Patients must have a performance status corresponding to Easter Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age. Patients must have a Karnofsky or Lansky score \>= 50%

• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately

‣ Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive

• Solid tumor patients: \>= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)

⁃ Anti-cancer agents not known to be myelosuppressive (eg, not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): \>= 7 days after the last dose of agent

⁃ Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1

⁃ Corticosteroids: If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid. Patients with CNS tumors receiving corticosteroids must have been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment

⁃ Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur

⁃ Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)

⁃ Stem cell Infusions (with or without total body irradiation \[TBI\]):

• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: \>= 84 days after infusion and no evidence of graft versus host disease (GVHD)

∙ Autologous stem cell infusion including boost infusion: \>= 30 days

⁃ Cellular therapy: \>= 42 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.)

⁃ Radiation therapy \[XRT\]/external beam irradiation including protons: \>= 14 days after local XRT; \>= 150 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial bone marrow (BM) radiation

⁃ Radiopharmaceutical therapy (e.g., radiolabeled antibody, I-131 metaiodobenzylguanidine \[131I MIBG\]): \>= 42 days after systemically administered radiopharmaceutical therapy

⁃ Patients must not have received prior exposure to CBL0137

• For patients with solid tumors without known bone marrow involvement:

‣ Peripheral absolute neutrophil count (ANC) \>= 1000/uL (performed within 7 days prior to enrollment unless otherwise indicated)

⁃ Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity

• For patients with solid tumors without known bone marrow involvement:

‣ Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (performed within 7 days prior to enrollment unless otherwise indicated)

⁃ Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity

• Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a creatinine based on age/sex as follows (performed within 7 days prior to enrollment unless otherwise indicated):

‣ Age: Maximum serum creatinine (mg/dL)

⁃ 1 to \< 2 years: 0.6 (male); 0.6 (female)

⁃ \>= 16 years: 1.7 (male); 1.4 (female)

• Patients with solid tumors:

‣ Bilirubin (sum of conjugated + unconjugated or total) =\< 1.5 x upper limit of normal (ULN) for age (performed within 7 days prior to enrollment unless otherwise indicated)

• Patients with solid tumors:

‣ Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L (performed within 7 days prior to enrollment unless otherwise indicated)

• Shortening fraction of \>= 27% by echocardiogram (performed within 7 days prior to enrollment unless otherwise indicated) or

• Ejection fraction of \>= 50% by gated radionuclide study (performed within 7 days prior to enrollment unless otherwise indicated)

• Corrected QT (QTC) \< 480 msec (performed within 7 days prior to enrollment unless otherwise indicated)

• Patients with seizure disorder may be enrolled if seizures well controlled without the use of enzyme-inducing anti-convulsant agents. Well controlled is defined by no increase in seizure frequency in the prior 7 days

• Nervous system disorders (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\]5) resulting from prior therapy must be =\< grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible

• Patients have consented to receive a central venous catheter prior to the administration of CBL0137. A central line is required for CBL0137 administration